With recent developments in technology, the effect of diabetes on the anterior segment can now be evaluated objectively. Within the anterior segment structures, the cornea has the greatest effect on sight prognosis. Direct damage to corneal cells (epithelium, stroma, endothelium), reduced corneal innervation, and impaired ocular surface homeostasis associated with dry eye, cause corneal pathologies. Impaired proliferation, migration, and adhesion of the corneal epithelium in particular leads to recurrent corneal erosions and persistent epithelial defects. All of these render the cornea more sensitive to minor trauma and pathogens. 12
Dry eye and ocular surface inflammation are often seen in diabetes, with consequent changes in tear production, stability and the quality of the lipid layer. Both microvascular damage of the lacrimal gland and reduced sensory innervation of the lacrimal gland as a result of neuropathy cause a reduction in tear secretion and a deficiency of aqueous tears. 7 A decreased number of goblet cells in the conjunctiva affects tear stability by decreasing mucin secretion. 7, 13 In addition, meibomian gland dysfunction, which is often seen in diabetic patients, causes deficiencies in the lipid layer and increases the evaporation of tears. 14, 15 Therefore, as each of the layers of tears is affected in diabetic patients, dry eye is seen more frequently. In the current study, the values of the Schirmer test, which evaluates tear secretion, and of the TBUT test, which evaluates tear stability, were determined to be lower in the diabetic patients than in the control group. However, no relationship was found with the duration of diabetes, the degree of DR, or the HbA1c level.
Corneal stromal hydration is kept in balance with the endothelial pump function and the epithelial barrier function. Chronic metabolic stress caused by hyperglycemia in the corneal epithelium, stroma and endothelium affects corneal thickness. 16 A reduction in the number of endothelial cells and impaired function especially cause an increase in CCT. 17 Conflicting results have been obtained in studies that have evaluated corneal thickness in diabetic patients. While some studies have shown that the CCT is thicker in diabetic patients than control subjects. 17–19 others have reported no significant difference. 20–23 This difference between studies may be due to the difference in the time of measurement and the device used, the metabolic status of the patient at the time of measurement, the duration of diabetes, the severity of retinopathy, and different ethnic origins.The results of the current study showed that the CCT was statistically significantly thicker in the diabetic patients than in the control group. The duration of diabetes, HbA1c level, and DR degree were not determined to have a significant effect on CCT. However, when the NDR, NPDR, and PDR groups were compared separately with the control group, the difference between them was seen to gradually decrease (p=0.205, p=0.535, p=1.00). As will be explained below, this was thought to be associated with the CCET decreasing as the DR degree increased.
The corneal epithelium is kept in continuous balance with limbal stem cell proliferation and migration corresponding to the loss of surface cells. To be able to maintain the integrrity of the corneal epithelium, in adddition to a healthy tear layer, healthy nerve innervation is necessary. Various neurotrophic factors that are expressed provide proliferation and differentiation of stem cells in the limbus. As a result of neuropathy developing in diabetic patients, a reduction in these neurotrophic factors causes epithelial fragility, recurrent corneal erosions and persistent epithelial defects. 24 Several studies have shown that the sub-basal nerve plexus (SBNP) is clearly affected in diabetic patients (a reduction in the number and length of nerve fibres, decreased branching, increased tortuosity). 25–27 Basal epithelial cell density (BECD) and epithelial thickness decrease together with the development of corneal neuropathy.25, 26, 28 These changes in the SBNP have been found to be related to peripheral neuropathy and diabetic retinopathy. 28–30 Rosenberg et al showed that the corneal epithelium was significantly thinner in patients with severe neuropathy compared to patients without neuropathy. 25 Nitoda et al reported that corneal neuropathy was related to peripheral neuropathy and the degree of DR,29 while Chang et al found that BECD was reduced together with DR, and this was in parallel to SBNP loss. 30 However, different results have been obtained in studies that have evaluated the effect of HbA1c level and the duration of diabetes on SBNP. Pellegrini et al showed that both parameters had an effect on changes in the SBNP, 31 while Kallinikos et al reported that there was no significant effect. 32 Lomoriello et al suggested that there was an inverse correlation with the duration of diabetes and the HbA1c level had no significant effect 33 while in contrast, Dehghani et al suggested that there was an inverse correlation with the HbA1c level, and there was no significant effect of the duration of diabetes.
In the current study, the CCET was determined to be statistically significantly thinner in the diabetic group compared to the control group. Although this decrease was not related to the duration of diabetes and HbA1c level, there was seen to be an inverse correlation with the degree of diabetic retinopathy. No significant difference was determined between the control group and the group without DR, and there was a significant difference between the control group and the patients with DR. As the degree of DR increased, so the CCET decreased. This showed that the difference between the control group and the diabetic group was due to the patients with retinopathy.
There may be 3 reasons for the decrease in CCET in diabetes: i) secondary to dry eye, which is common in diabetic patients, ii) impaired epithelial homeostasis associated with corneal neuropathy, and iii) the effect of retinal photocoagulation (RP). There has been a recent increase in studies evaluating the effect of dry eye on the corneal epithelium. Trauma occurring when blinking associated with reduced lubrication in dry eye, impaired feeding of the epithelial cells, and an increase in inflammation, affect the corneal epithelium. Some studies have shown that the epithelium is thinner in patients with dry eye, 35–38 some that there is no change, 39 and some that it has even increased. 40, 41 As dry eye is frequently seen in diabetic patients, it may be a factor in the decrease in CCET. In the current study, although dry eye was seen more often in diabetic patients, no significant difference was determined between those with and without DR. Therefore, as the severity of dry eye does not increase with the severity of DR, even if there is a partial effect, this was not thought to be the main reason. There are studies in literature showing that by increasing corneal neuropathy, RP reduced epithelial thickness, 30 or had no effect. 42 As RP had been applied to all the current study patients with PDR, the NPDR and PDR groups were compared and no significant difference was determined. The main reason for the decrease in CCET was thought to be the increase in the degree of corneal neuropathy together with the DR degree, as has been shown in previous studies. That CCET was not found to be correlated with the duration of diabetes and the HbA1c level suggested that these parameters had no effect on the development of corneal neuropathy, as reported by Kallinikos et al. This is perhaps because of the low reliability of HbA1c level and diabetes duration data in evaluating the long-term effect of diabetes on the eye. Because the HbA1c level is a cross-sectional measurement, it only provides information about blood glucose levels in the last 3 months and may not show long-term metabolic control. Since the duration of diabetes is determined based on the patient's statement, it may not reflect the actual duration. Therefore, the degree of diabetic retinopathy provides us with more objective information.
In conclusion, the epithelial layer is the first part of the cornea to be exposed to environmental factors and has an important place in ensuring corneal integrity. Corneal epithelial pathologies may be seen more frequently in patients with advanced diabetic retinopathy due to reduced corneal epithelial thickness. Early and effective treatment should be initiated in these patients, as epithelial defects that occur after simple trauma or surgery may cause greater problems.