Background: Diabetes mellitus is a chronic condition characterized by elevated blood glucose levels and is commonly associated with ocular complications, including diabetic retinopathy, cataracts, and glaucoma. One under-explored aspect of diabetes is diabetic keratopathy, which involves changes to the corneal structure, including alterations in central corneal thickness (CCT). The aim of this study was to investigate the relationship between diabetes mellitus and CCT in patients attending a tertiary care center. Methods: A case-control study was conducted involving 100 diabetic and 100 non-diabetic patients, with 50 participants in each group. Central corneal thickness was measured using ultrasound pachymetry. The study assessed the impact of gender, duration of diabetes, and glycemic control (HbA1c levels) on CCT. Results: The mean CCT was significantly higher in diabetic patients (564.54 ± 24.56 µm) compared to non-diabetic controls (519.45 ± 25.98 µm, P < 0.002). No significant gender differences were observed in CCT among diabetic patients (578.87 ± 30.12 µm for males and 551.78 ± 29.11 µm for females, P = 0.256). A positive correlation between CCT and diabetes duration was found, with longer duration correlating with thicker corneas. However, no significant association was found between CCT and glycemic control (P = 0.231). Conclusion: The study found a significant increase in CCT in diabetic patients compared to non-diabetic individuals. Though the duration of diabetes influenced corneal thickness, glycemic control did not show a significant effect. The findings suggest that CCT may serve as a useful indicator in managing diabetic patients, particularly in preoperative assessments and glaucoma evaluations. Further investigation into the relationship between diabetic keratopathy and corneal ectatic disorders is warranted.
Diabetes mellitus is a medical condition characterised by elevated blood glucose levels, referred to as hyperglycemia. This syndrome is generally associated with chronic complications impacting both microvascular and macrovascular systems. Individuals with diabetes mellitus often experience keratoepitheliopathy, characterised by persistent epithelial defects, recurrent corneal erosion, and superficial punctate keratitis, alongside diabetic retinopathy [1, 2]. The main manifestations of diabetes in ocular tissues include retinopathy, cataracts, and glaucoma. Diabetic keratopathy, a relatively under-researched condition, pertains to the corneal alterations observed in individuals with Diabetes mellitus [3]. The condition may present in multiple forms, including diminished corneal sensitivity, epithelial disorders such as superficial punctate keratitis and epithelial erosions, and a thickened basement membrane [4,5]. Increased concentrations of glycosylated haemoglobin in the blood correlate with a heightened vulnerability to compromised corneal epithelial barrier function. The use of glucose as a collagen cross-linking agent is enabled by advanced glycosylation end products. The aggregation of advanced millard products in collagen proteins results in the establishment of covalent cross-linking bonds, which may contribute to corneal thickening and related biochemical changes [6]. Increased levels of glycosylated haemoglobin in the blood may impair the integrity of the corneal epithelial barrier [7]. Collagen cross-links may be generated by glucose in the presence of advanced glycation end products. The authors claim that there is an increase in covalent bonding within the corneal stroma, which may lead to a rise in corneal thickness [8]. Corneal hydration results from the intracellular buildup of sorbitol, which acts as an osmotic agent, as demonstrated by multiple studies. The inhibition of Na+K+ ATPase activity suppresses corneal endothelial pump function, resulting in increased corneal thickness. The corneal endothelium in diabetic individuals is considered a tissue subjected to continuous metabolic stress. This condition is marked by a heightened coefficient of variation in endothelial cell area, a diminished percentage of hexagonality, and an elevated level of corneal autofluorescence [9,10]. The assessment of central corneal thickness serves as a sensitive indicator of corneal health, providing a crucial metric for evaluating corneal hydration and metabolism. Moreover, it is a crucial factor influencing the efficacy of the corneal endothelium pump, and its evaluation can be performed using several objective methods, including optical pachymetry, ultrasound pachymetry, confocal microscopy, ultrasound biomicroscopy, optical ray path analysis, scanning slit corneal topography, and optical coherence tomography [11]. The prevailing gold standard for assessing corneal thickness is ultrasound pachymetry [12]. This study aimed to examine the relationship between type 2 diabetes mellitus and central corneal thickness in patients receiving treatment at Gouri Devi medical college Durgapur.
The researchers secured ethical approval from the institutional ethics committee to conduct a case-control study at Gouri Devi medical college Durgapur.The study included one hundred individuals diagnosed with diabetes by medical professionals. Participants were enrolled irrespective of their current treatment status or blood glucose levels, contingent upon their provision of informed consent. The study also included one hundred age-matched individuals devoid of a diabetes history and possessing normal blood sugar levels. Individuals with corneal pathologies, including pterygium and corneal dystrophies, contact lens users, those receiving treatment for topical or systemic conditions, and individuals with a history of ocular surgeries were excluded from the study. A thorough evaluation of the anterior and posterior segments was performed. The evaluation of corneal thickness was performed on 100 eyes, comprising 50 eyes from diabetic patients and 50 eyes from non-diabetic patients. This assessment was conducted with an ultrasound pachymeter, specifically the Sonomed Pacscan Plus, employing the multiple reading single point mode. All measurements were conducted by a single individual. The final measurement was ascertained by computing the average of five readings, each exhibiting a standard deviation of under 0.003mm.
The mean age of the study participants was 45.85 years. Figure 1 indicates that 54% of the participants were classified as male, whereas the remaining 46% were classified as female. More than 40% of participants in both case-control studies were aged 41-50.
Table 1: Mean CCT in Diabetics (Case) and Non-Diabetics (Control) with Gender Distribution
Patients |
N |
Mean CCT (µm) |
SD (±) |
P-value |
95% CI |
Gender Distribution |
Diabetic |
50 |
564.541 |
24.56 |
<0.002 |
4.4 - 8.9 |
50% Male, 50% Female |
Non-diabetic |
50 |
519.453 |
25.98 |
50% Male, 50% Female |
The average central corneal thickness (CCT) for the entire study group was 527.341 ± 30.56 µm. Diabetic patients had a mean CCT of 564.541 µm, significantly higher than the mean CCT of 519.453 µm in the non-diabetic group (P-value < 0.002). The 95% confidence interval (CI) for the difference in CCT between the two groups was 4.4 to 8.9 µm. The gender distribution for both groups was balanced, with 50% males and 50% females in each group.
Table-2: Gender distribution with mean CCT in diabetic group |
||||
Gender |
n |
Mean CCT (µ) |
SD (±) |
P value |
Male |
35 |
578.87 |
30.12 |
P=0.256 |
Female |
15 |
551.78 |
29.11 |
The table indicates that the average corneal cross-linking time (CCT) in male diabetic patients (578.87± 30.12µ) was greater than that of female patients (551.78± 29.11µ). Nonetheless, this disparity was not statistically significant, as evidenced by a p-value of 0.256 (Table 2). Individuals diagnosed with diabetes and HbA1c levels below 6.5% demonstrated a central corneal thickness (CCT) of 548.22 ± 21.7 µm. In contrast, individuals with HbA1c levels above 6.5% exhibited a greater CCT of 568.12 ± 27.5 µ. Nonetheless, it is crucial to acknowledge that the difference in CCT between the two groups was not statistically significant (p = 0.231) as indicated in Table 2.
Table-3 : Central corneal thickness with duration of diabetes and with glycemic control |
||||||
Duration of diabetes |
n |
Mean CCT (µ) |
SD (±) |
X2 |
P value |
|
<10 yrs
|
<5 yrs
|
16 |
548.76 |
25.78 |
2.178 |
P=0.115 |
5-10 yrs |
44 |
|||||
≥10 yrs |
40 |
576.89 |
16.87 |
The preceding table illustrates In a sample of 100 individuals diagnosed with diabetes, a substantial percentage demonstrated a diabetes duration between 5 and 10 years, with a mean duration of 9.478±1.7 years. The average central corneal thickness (CCT) in individuals with diabetes for over 10 years was higher (576.89 ±16.87µ) than in those with a duration of less than 10 years (548.76 ±25.78 µ), indicating a positive correlation. Nonetheless, statistical analysis revealed that this difference was not statistically significant (p=0.115).
Table-4: Central corneal thickness with glycemic control |
|||||
HbA1c |
n |
Mean CCT (µ) |
SD (±) |
P-value |
95%CI |
<6.5% |
19 |
548.12 |
21.7 |
P=0.231 |
7.8-25.36 |
>6.5% |
6 |
568.22 |
18.5 |
FiftyThe preceding table illustrates In a sample of 50 individuals diagnosed with diabetes, a substantial percentage demonstrated a diabetes duration between 5 and 10 years, with a mean duration of 9.478±1.7 years. The mean central corneal thickness (CCT) in diabetic individuals with a disease duration exceeding 10 years was higher (576.89 ±16.87µ) than in those with a duration of less than 10 years (548.76 ±25.78 µ), indicating a positive correlation. Nonetheless, statistical analysis revealed that this difference lacked statistical significance (p=0.115).
Diabetic keratopathy denotes a spectrum of corneal alterations that manifest in individuals with diabetes. Our study indicated that individuals diagnosed with diabetes exhibit a statistically significant elevation in mean central corneal thickness relative to those without diabetes. Numerous hypotheses exist to elucidate this phenomenon. Numerous studies have indicated that a reduction in Na+K+ATPase activity directly impairs the operation of the corneal endothelial pump. In contrast, other studies have clarified that the intracellular accumulation of sorbitol, an osmotic agent, results in corneal hydration. Recent studies suggest that advanced glycosylated end products (AGEs) may act as cross-linking agents, enhancing covalent bonding within the corneal stroma and consequently increasing its thickness. The corneal confocal microscopy (CCM) technique in diabetic individuals offers significant insights into the functional and morphological status of the cornea.[13] The measurement in question is recognised as a reliable indicator of early diabetic keratopathy and is deemed a significant parameter for refractive surgery and the assessment of intraocular pressure (IOP).[14] The average central corneal thickness (CCT) of the entire cohort was found to be 527.341 ± 30.56µ in this investigation. This finding demonstrates a significant difference compared to the results from a previous study by Nangia et al., which reported a mean CCT of 514 ± 33.0µ for Indian eyes.Fifteen Their findings indicate that individuals from rural central India possess notably thinner corneas than both Caucasian and Chinese populations. The incorporation of a greater percentage of individuals from urban locales in our study, particularly within a tertiary eye centre, may elucidate the discrepancies in results relative to prior studies. The correlation between CCT and diabetes mellitus has been recorded with inconsistent results across numerous studies.[16, 17] Our investigation revealed that the average central corneal thickness (CCT) in individuals with diabetes was 565.98±30.02µ, whereas in those without diabetes it was 514.56±30.02µ. A statistically significant difference was observed between the two groups (p-value 0.0124, Mann-Whitney test). In a similar study, Claramonte et al. established a significant association between diabetes and central corneal thickness (CCT). The mean central corneal thickness (CCT) in diabetic individuals in the study was 571.96µ, while non-diabetic individuals exhibited an average CCT of 544.89µ. The disparity was found to be statistically significant.17 Conversely, Keoleian et al. conducted a study to evaluate the structural and functional status of the corneal endothelium in diabetic individuals. Their findings led to the conclusion that, despite structural abnormalities, the functional integrity of the corneal endothelium remained intact in this population.[18] The researchers noted no statistically significant difference in corneal thickness among individuals with diabetes. A supplementary study performed in Japan similarly revealed no significant correlation between central corneal thickness (CCT) and diabetes.[19] The mean central corneal thickness (CCT) for male participants in the diabetic cohort was 528.87± 30.12µ, which exceeded that of female participants at 521.78± 29.11µ. In contrast, within the non-diabetic cohort, male participants exhibited a lower average central corneal thickness (CCT) of 519.65± 28.41µ compared to their female counterparts, who had an average CCT of 524.89± 26.19µ.No statistically significant difference was observed in either group, with p-values of 0.32 and 0.54, respectively. A recent study on Indian individuals has demonstrated a significant difference in central corneal thickness (CCT) between males (515.6 ± 33.8µ) and females (508.0 ± 32.8µ), with a statistically significant p-value of 0.001.[20] Lee et al. performed a study to examine the effect of diabetes duration on corneal thickness. The research findings indicated that individuals with diabetes for over 10 years demonstrated a greater prevalence of corneal morphological abnormalities than those without diabetes.In our study, we found that the average central corneal thickness (CCT) in individuals with diabetes for over 10 years was significantly greater (544.64±34.56µ) than in those with diabetes for less than 10 years (518.98±31.21µ). McNamara et al. (year) conducted a study that identified a positive correlation between HbA1c levels and central corneal thickness (CCT) in individuals with Type 1 diabetes. Furthermore, they observed increased corneal thickness in individuals with diabetes. Nonetheless, they did not identify a direct correlation between HbA1c levels and CCT in individuals with Type 2 diabetes, which is consistent with the results of our study.[22] Yasgan et al. further validated this observation.[23]
A significant correlation was identified between the increase in central corneal thickness (CCT) and the existence of diabetes. A positive correlation was observed between corneal thickness and diabetes duration, indicating that individuals with thicker corneas are more likely to receive a diagnosis at a later stage of the disease. The obligatory assessment of central corneal thickness (CCT) in diabetic patients is essential in several clinical contexts, including preoperative evaluations for refractive surgery, assessment of donor tissue before keratoplasty, individuals suspected of glaucoma, and long-term contact lens users. This method may aid in identifying patients at high risk for severe complications, allowing ophthalmologists to provide more targeted treatment for their conditions. The evaluation of central corneal thickness (CCT) alongside the examination of the corneal endothelium can provide supplementary critical information for the precise assessment of patients regarding their functional outcomes. Considering that the primary histopathological change entails the formation of covalent bonds within the corneal stroma, it is crucial to explore the possible relationship between diabetic keratopathy and corneal ectatic disorders.