Neurodegeneration in Patients with Type 2 Diabetes Mellitus without Diabetic Retinopathy

Abstract

Purpose. To evaluate neurodegeneration in patients with type 2 diabetes mellitus (DM2) without diabetic retinopathy and to assess the possible role of systemic vascular complications in retinal changes. Methods. Sixty eyes of 60 patients with DM2 and without any signs of diabetic retinopathy and 60 eyes of 60 healthy controls underwent retinal evaluation using Spectralis optical coherence tomography. Macular ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) were evaluated. Peripapillary RNFL thickness was assessed using Glaucoma and Axonal Analytics applications. Comparison between patients with the presence/absence of systemic vascular complications and different disease duration was made. Results. Macular GCL was reduced in patients compared to controls (p<0.001). Differences in the macular RNFL thickness were only observed in the outer inferior sector (p=0.033). A reduction in the peripapillary RNFL (average, inferior, and inferotemporal thickness, p<0.05 for all three) was observed in patients using both applications. Patients with chronic systemic vascular complications presented a reduction in the temporal RNFL (p=0.019) compared to patients without complications. The superotemporal RNFL thickness was thinner in patients with longer disease duration. Conclusions. Patients with type 2 DM without diabetic retinopathy and good metabolic control present neurodegeneration affecting neurons in the macular area and axons in different sectors of the optic disc. Systemic vascular complications contributed to further axonal damage in these patients, suggesting a possible role of subclinical ischaemia to retinal neurodegeneration in type 2 DM.

Early Identification of Retinal Neuropathy in Subclinical Diabetic Eyes by Reduced Birefringence of the Peripapillary Retinal Nerve Fiber Layer

“…There are studies showing evidence of GCL and IPL thinning in diabetics 38,39 even in the absence of any DR, 2,38,40 whereas Verma et al 41 report thicker GCL layers in diabetic subjects compared with healthy controls. Loss of RNFL in diabetic eyes with no to minimal DR compared with controls was shown, 2,42 with other studies demonstrating no differences in diabetic eyes. 41,43 Macular thickness in diabetic patients varies greatly with disease progression already in subclinical stages and even more when macular edema develops.…”

Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone

“…In diabetes a subclinical ischaemia is suggested to have a possible, important role in retinal neurodegeneration, furthermore this neurodegeneration is also present without developed diabetic retinopathy and even in patients with good metabolic control [56]. Oxidative stress alone is able to trigger the c-Jun amino-terminal kinase (JNK) mitogen-activated protein (MAP) kinase pathway, which-by enhancement of mitochondrial outer membrane permabilization (MOMP) [57] and formation of mitochondrial permeability transition pores (MPTP) [58]-leads to the damage of the mitochondrial membrane letting out proapoptotic mediators and perhaps MMP9.…”

Retinal Vascular Endothelial Cell Dysfunction and Neuroretinal Degeneration in Diabetic Patients

“…In addition, patients with type 2 diabetes with no diabetic retinopathy but good metabolic parameters exhibited neurodegeneration affecting neurons in the macula and axons in the optic nerve. Systemic vascular changes led to further damage of the axons and indicated a potential role of subclinical ischemia in retinal neurodegeneration appearance [ 121 ].…”