A systematic review on the impact of diabetes mellitus on the ocular surface

K Co Shih, K S-L Lam, L Tong, K Co Shih, K S-L Lam, L Tong

Abstract

Diabetes mellitus is associated with extensive morbidity and mortality in any human community. It is well understood that the burden of diabetes is attributed to chronic progressive damage in major end-organs, but it is underappreciated that the most superficial and transparent organ affected by diabetes is the cornea. Different corneal components (epithelium, nerves, immune cells and endothelium) underpin specific systemic complications of diabetes. Just as diabetic retinopathy is a marker of more generalized microvascular disease, corneal nerve changes can predict peripheral and autonomic neuropathy, providing a window of opportunity for early treatment. In addition, alterations of immune cells in corneas suggest an inflammatory component in diabetic complications. Furthermore, impaired corneal epithelial wound healing may also imply more widespread disease. The non-invasiveness and improvement in imaging technology facilitates the emergence of new screening tools. Systemic control of diabetes can improve ocular surface health, possibly aided by anti-inflammatory and vasoprotective agents.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic showing pathogenesis of corneal disease in diabetes mellitus. Hyperglycemia and formation of advanced glycation end products have distinct effects on different parts of the cornea, resulting in three principal types of tissue dysfunction with physiological effects that can be measured. (1) Defective wound healing in the corneal epithelium, (2) abnormalities of sub-basal nerves and (3) loss of corneal endothelial pump function. (1) Raised blood glucose promotes IGFBP3 release, which in turn competitively inhibits IGF-1, whereas TGFb3, EGFR, CNTF are suppressed in hyperglycemic states. The consequential reduction in epithelial cell proliferation and increased apoptosis impacts on epithelial wound healing. (2) Neuronal damage is a key defect in diabetes mellitus. Prolonged hyperglycemia results in the accumulation of advanced glycation end products which promotes inflammation and oxidative stress. NGF and sphingolipids are key to neuronal health and myelin formation, but their production are inhibited in hyperglycemic states. (3) Prolonged hyperglycemia also results in endothelial cell loss and impairment in pump function. Apart from these processes, the swelling of the corneal stroma (the main bulk of the cornea) may be due to loss of epithelial barrier, crosslinking of stromal collagen and matrix, and loss of the endothelial pump. CNTF, ciliary neurotrophic factor; EGFR, epithelial growth factor receptor; IGF-1, insulin-like growth factor 1; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells transcription factor; NGF, nerve growth factor; TGFb3, transforming growth factor beta-3. Solid blue arrows—activation/promotion, red stop arrows—inhibition or negative regulation.

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Source: PubMed

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