Early Corneal Cellular and Nerve Fiber Pathology in Young Patients With Type 1 Diabetes Mellitus Identified Using Corneal Confocal Microscopy

Abstract

Corneal confocal microscopy identifies corneal cellular and small nerve fiber pathology in young patients with type 1 diabetes without retinopathy, which increases in severity in those with retinopathy. Corneal confocal microscopy appears to have considerable use as an imaging biomarker for early subclinical pathology in young patients with type 1 diabetes mellitus.

Diabetic complications in the cornea

“…Signs of diabetic keratopathy include epithelial fragility, defects and recurrent erosions, non-healing ulcers, corneal edema due to altered epithelial barrier function, superficial punctate keratitis, abnormally slow and often incomplete wound healing, lower cell density especially in the basal layer, and increased susceptibility to injury (Ben Osman et al, 1995; Saini and Khandalavla, 1995; Ohashi, 1997; Sánchez-Thorin, 1997; Inoue et al, 2001; Cavallerano, 2002; Gekka et al, 2004; Quadrado et al, 2006; Wylegała et al, 2006; Szalai et al, 2016; Vieira-Potter et al, 2016). The data on the prevalence of diabetic keratopathy depending on the type of diabetes remain inconsistent and need to be revisited (Schultz et al, 1981; Didenko et al, 1999).…”

“…This symptom is related to abnormalities of corneal nerve structure and function in diabetes. Detailed examination including the use of in vivo confocal microscopy has revealed abnormalities in nerve fiber density, length and branch density, as well as increased nerve tortuosity and thickness in human diabetic corneas (Rosenberg et al, 2000; Malik et al, 2003; Kallinikos et al, 2004; Mocan et al, 2006; De Cillà et al, 2009; Szalai et al, 2016). These alterations may be worsened after laser photocoagulation in PDR (De Cillà et al, 2009).…”

“…The sub-basal nerve alterations in diabetic mice are accompanied by abnormalities of dendritic cells that may serve neurotrophic functions (Leppin et al, 2014; Gao et al, 2016). Several studies have documented corneal neuropathy early in diabetes, before the development of DR (Zhivov et al, 2013; Papanas and Ziegler, 2013; Petropoulos et al, 2015; Szalai et al, 2016). Moreover, in rat models, corneal nerve damage occurred not only in animals with NIDDM but also in those that were obese but non-diabetic, suggesting that corneal neuropathy may develop even before the onset of hyperglycemia (Davidson et al, 2014) and calling for therapeutic interventions in pre-diabetes.…”

Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats

“…Poor outcomes may be correlated with the consistently rising prevalence of chronic illnesses among PNI patients including diabetes mellitus (DM), which is expected to affect 591.9 million patients by 2035 [4]. Long standing hyperglycemia, a common manifestation of DM, significantly complicates treatment outcomes due to its direct impact on nervous system function [5,6], resulting in axonal atrophy, segmental demyelination, and slow regeneration of injured nerves [7,8]. Studies have shown that, compared with normal mice, diabetic mice are more susceptible to deficits in axonal regrowth after acute crush of the sciatic nerve [9], and clinically, treatments capable of inducing complete functional recovery of injured peripheral nerves in diabetics remain elusive.…”

Widespread effects of clinically unilateral focal nerve injuries

“…[4-6; 8; 9; 28] Focal trigeminal lesions and systemic “small-fiber” polyneuropathies both cause clearly detectable damage. [7; 21; 24] For instance, we used IVCM to analyze corneal innervation in both eyes of 27 patients with unilateral V 1 herpes zoster ophthalmicus (HZO) and 31 with V 1 herpes simplex virus (HSV) and healthy controls. [8; 9] Both diseases caused reductions in the number and density of corneal neurites (depicted in Fig.…”