The onset of diabetes mellitus (DM) causes multiple damages to the ocular surface and there are many studies published in the last 10 years dealing with the correlation.
The relationship between diabetes and the eyes was published this month in the journal Nutrition and Diabetes, the first systematic review which provided a comprehensive overview of the consequences of DM on the ocular surface and cornea.
Below - in the same order in which they are published in the prestigious journal Nature - are the implications for each distinct ocular district.
Diabetes and the eyes: the consequences for each eye district
Ocular surface abnormalities and pathologies of the corneal epithelium
The eyes of diabetic patients - as known - are at greater risk of dryness, superficial keratitis punctata, corneal erosion syndrome and persistent epithelial defects. Moreover, since diabetes is associated with a decrease in healing of micro-lesions and since the corneal epithelium is a layer of the eye that is constantly subjected to wear and tear, the lack of constant cell regeneration has a major physiological impact on the eye, increasing its inherent morbidity, sensitivity to pain and ease of redness.
Recently, a study in vivo showed for the first time that the tear levels of both type 1 and type 2 diabetic individuals were significantly higher of insulin-like growth factor binding protein (IGFBP3), a protein that appears to be correlated with apoptosis, oxidative stress and insulin resistance. The specific role of this protein at the ocular level is still poorly understood, however it seems that a state of hyperglycaemia promotes its synthesis. As for the negative effects on the basal epithelium of the corneal membraneseveral studies in mouse models have confirmed that hyperglycaemia is a triggering factor.
In these studies, the decreases in epithelial function were documented by an increase in corneal thickness and structural changes were examined by electron microscopy. Since the corneal epithelium performs an important barrier function to exclude water from the stroma, a reduction in its 'barrier function' is manifested by the onset of oedema.
But, exactly what happens under these circumstances to the corneal epithelium?
The epithelium component that forms the stromal barrier is largely made up of complexes of corneous epithelial cells connected by tight junctions and visualised as electrondense structures. The loss or rupture of these joints is the basis of the loss of epithelial function, which in turn can affect vision due to the opacification of the cornea and the difficulty of transmitting light through it.
Corneal neuropathy
The cornea is the most innervated structure in humans; its nerve fibres play an important neurotrophic role in the development of a healthy corneal surface, epithelial integrity and healing capacity. Loss of neurotrophic function of the cornea can result in a persistent corneal epithelial defect or neurotrophic ulcers with serious implications for visual function. Recently, both types of DM have been associated with reduced density and other abnormalities of the corneal nerves, which are branches of the optic nerve; moreover, alterations in corneal nerve parameters have been correlated with the onset of both diabetic and autonomic peripheral neuropathy.
The most important advance in recent years in the analysis of corneal innervation is laser scanning ophthalmoscopy. The captured images are processed by a software of imaging to assess nerve fibre or nerve branch density, nerve length and nerve tortuosity in the sub-basal plexus because changes in this layer are more relevant in DM patients than structural changes in intrastromal nerves.
Finding specific density or length indices in a given region of the cornea is often correlated with specific clinical scenarios. For example, it has been shown that nerve fibre density in the lower corneal region is more sensitive to early damage than in the central corneal region in DM patients before the development of peripheral neuropathy.
But, is good glycaemic control sufficient to limit corneal nerve dysfunction? Two clinical cohort studies established that good glycaemic control is, in fact, able to improve but not completely reverse corneal neuropathy.
Corneal stroma
The stroma, the corneal structure beneath the epithelium and Bowman's layer, accounts for 90% of the corneal thickness and is therefore important for its tensile strength and biomechanical properties. The main novelty in recent clinical studies on corneal biomechanics concerned the assessment of corneal hysteresis and tensile strength thanks to the recent availability of the Ocular Response Analyzer systemwhich can quantify these two parameters. A higher hysteresis value suggests a stiffer and less deformable cornea.
Indeed, several studies have reported that participants with type 1 and type 2 DM have higher hysteresis than age-matched controls. The reason why DM is associated with increased corneal hysteresis or thickness has not yet been fully elucidated, however, it has been hypothesised that an accumulation of advanced glycation end products (AGEs) in the stratum corneum of diabetics, together with a cross-linking between collagen molecules and proteoglycans.
The accumulation of AGEin particular, has an important pathological outcome as it is considered the mediator of all DM complications including macrovascular and microvascular ones, such as the diabetic retinopathy in the eye, since shifts local cell signalling towards pro-apoptotic and anti-proliferative pathways and increases oxidative stress and inflammatory status.
Pathologies of the corneal endothelium
In addition to the epithelium, the innermost layer of the cornea, called corneal endothelium, plays a key role in the keep the stroma dehydrated. This is due to the active action of corneal endothelial cells that pump fluid from the cornea to the anterior chamber. In several studies, a not always significant increase in morphological abnormalities, in terms of cell size and greater variability of shape, of the corneal endothelium, especially after operations of cataract.
So, ocular surface and corneal parameters are important for screening patients. However, as many of these factors are closely linked to age, the widespread use of these indices will only be useful if the values will be normalised and stratified. In addition, the use of imaging techniques increasingly advanced will be crucial for the study of structural changes in individuals with DM and diabetic neuropathy.
Bibliography
Dr. Carmelo Chines
Direttore responsabile
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