Diabetic Corneal Neuropathy

Abstract

Diabetic keratopathy (DK) is a common, but underdiagnosed, ocular complication of diabetes mellitus (DM) that has a significant economic burden. It is characterised by progressive damage of corneal nerves, due to DM-induced chronic hyperglycaemia and its associated metabolic changes. With advances in corneal nerve imaging and quantitative analytic tools, studies have shown that the severity of diabetic corneal neuropathy correlates with the status of diabetic peripheral neuropathy. The corneal nerve plexus is, therefore, considered as an important surrogate marker of diabetic peripheral neuropathy and helps in the evaluation of interventional efficacy in the management of DM. The clinical manifestations of DK depend on the disease severity and vary from decreased corneal sensitivity to sight-threatening corneal infections and neurotrophic ulcers. The severity of diabetic corneal neuropathy and resultant DK determines its management plan, and a step-wise approach is generally suggested. Future work would focus on the exploration of biomarkers for diabetic corneal neuropathy, the development of new treatment for corneal nerve protection, and the improvement in the clinical assessment, as well as current imaging technique and analysis, to help clinicians detect diabetic corneal neuropathy earlier and monitor the sub-clinical progression more reliably.

Keywords: corneal nerves; diabetes mellitus; diabetic keratopathy; diabetic neuropathy; neurotrophic keratopathy.

Figure 1

A three-dimensional section of the human cornea depicting the corneal nerve density and width at different layers. The figure has been created with BioRender.com.

Figure 2

Clinical manifestations of neurotrophic keratopathy (NK). (a) A persistent oval corneal epithelial defect with smooth and rolled edges. (b) The neurotrophic ulcer has been stained with 2% w/v solution of fluorescein sodium (c) Secondary microbial infection of the neurotrophic corneal ulcer with a hypopyon in the anterior chamber.

Figure 3

In-vivo confocal images of the subbasal nerve plexus of the (a) non-diabetic, (b) Type 1 diabetic and (c) Type 2 diabetic individuals. In both Type 1 and Type 2 diabetic patients, the corneal nerve fibre density, nerve fibre length, and total branch density are decreased compared to non-diabetic subjects. The nerves are more tortuous in patients with DM compared to controls.

Figure 4

In-vivo confocal images of the inferior whorl of corneal nerves of the (a) non-diabetic and (b) diabetic individuals. The length and density of the inferior whorl fibres are decreased in patients with DM compared to non-diabetics.

Figure 5

Surgical management of NK. (a) Amniotic Membrane Transplantation (b) Lamellar Corneal Transplant. The lack of trophic support, due to surgery-induced corneal denervation may impair epithelial wound healing and result in a persistent corneal epithelial defect, as shown by the black arrow.