Comparison of the central corneal thickness among diabetic and non-diabetic patients

INTRODUCTION

Diabetes mellitus (DM) is becoming one of the fastest-growing world health problems of the 21^st century and can not only be life-threatening but also a major cause of blindness if not properly controlled.^[1] It is a metabolic disorder characterised by hyperglycaemia resulting from absolute or relative insulin deficiency with dysfunction in various organs.^[1] The chronic hyperglycaemia of diabetes is associated with long-term damage and dysfunction of various organs such as the eyes, kidneys, nerves, heart and blood vessels.^[2]

In 2019, the worldwide prevalence of DM in persons aged 20 to 70 years was approximately 463 million.^[3] DM is more common in developed countries such as the United States, but low and middle-income countries are beginning to experience a steady rise in its prevalence.^[4] This increase is said to result from an increase in urbanisation with lifestyle modification, which entails an increase in consumption of high-energy but nutrient-deficient foods.^[4,5] There has also been an increase in the prevalence of DM in Nigeria. The Nigerian national blindness survey revealed a diabetes prevalence of 3.3% in those 40 years and above, 48% of whom were newly diagnosed during the survey in 2009.^[6] By 2018, a systematic review and meta-analysis by Uloko et al. showed an overall increase in prevalence of about 5.77%.^[7]

There are several ocular signs seen in diabetics, some of which include ocular surface diseases, cataract and diabetic retinopathy.^[8] The cornea is not spared as it undergoes morphological and functional changes leading to diabetic keratopathy.^[9] Diabetic keratopathy consists of recurrent corneal erosions, persistent epithelial defects, decreased corneal sensitivity and endothelial dysfunction.^[9,10] It has been noted that the functional changes seen in a diabetic cornea can result in an increased central corneal thickness (CCT).^[11] There are currently two major theories in support of this increase.^[11] The first theory indicates a structural change in the corneal stroma, which occurs from collagen cross-linking as a result of the accumulation of advanced glycation products in the collagen protein, leading to an increase in the thickness of the cornea.^[12] Secondly, in people with diabetes, sorbitol accumulates within the endothelial cells of the cornea with a reduction in the function of Na⁺ K⁺ATPase enzyme, leading to an increase in corneal hydration and corneal thickness.^[13,14] All these factors may indicate that an increase in the corneal thickness may be partly related to the functional status of the corneal endothelial layer.

CCT can be measured using several instruments, such as an optical pachymeter, an ultrasound pachymeter, confocal microscopy and anterior segment optical coherence tomography.^[12] Ultrasound pachymeter is the current gold standard for measurement of CCT.^[13]

MATERIALS AND METHODS

The study was carried out at the Endocrinology and Ophthalmology clinics of Lagos State University Teaching Hospital (LASUTH), Ikeja. Approval to conduct this study was obtained from the LASUTH Medical and Health Research Ethics Committee. The study was carried out in accordance with the ethical principles set out in the Declaration of Helsinki and the National Code for Health Research Ethics in Nigeria.

It was a cross-sectional, hospital-based study conducted over 1 year. A total of 140 patients were recruited; 70 diabetic and 70 non-diabetic age-matched controls were recruited.

Patients who had glaucoma, previous ocular surgeries, high myopia and cornea pathologies such as pterygium, corneal dystrophies and previous ocular surgeries were excluded from the study.

RESULTS

A total of 140 participants (70 diabetics and 70 non-diabetics) were studied. The majority (35.7%) of the participants in each group were aged 61–70 years of age. The mean age was 60.60 ± 12.4 years for people with diabetes and 59.87 ± 13.2 years for the non-diabetics. Age and sex distribution were similar by design. Overall, 72.9% (102 participants) of study participants were females and 27.1% (38) were male [Table 1].

The average CCT was 520.74 ± 49.8 µm in people with diabetes and 524.62 ± 28.7 um in the non-diabetics with no statistically significant difference (p = 0.572) [Table 2].

The median duration of diabetes was 8 years (range: 1–34 years). Amongst people with diabetes, 31 (44.3%) had good glycaemic control (glycated haemoglobin [HbA1c] < 6.5%), whereas 39 (55.7%) were poorly controlled [Figure 1].

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Figure 1: Duration since diagnosis of diabetes mellitus. The median duration of diabetes was 8 years (range: 1-34 years). Among diabetics, 31 (44.3%) had good glycaemic control (HbA1c < 6.5%) while 39 (55.7%) were poorly controlled.

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Thirty-one (44.3%) of the 70 diabetic participants had good glycaemic control as defined by a glycosylated haemoglobin value of <6.5%, and 39 (55.7%) were poorly controlled [Figure 2].

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Figure 2: The diabetic control status amongst the diabetic participants. Thirty-one (44.3%) of the 70 diabetic participants had good glycaemic control as defined by glycosylated haemoglobin value of < 6.5% and 39 (55.7%) were poorly controlled.

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No significant correlation was found between HbA1c and CCT (Pearson r = 0.090, p = 0.481) [Figure 3]. CCT was slightly higher in poorly controlled diabetics compared to controlled diabetics, but not statistically significant (p = 0.881). IOP was slightly lower in uncontrolled diabetics, though this difference was not significant (p = 0.067) [Table 3].

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Figure 3: Correlation between glycated haemoglobin and central cornea thickness. Pearson correlation = 0.090, p = 0.481. CCT: Central corneal thickness

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CCT was higher in participants with a diabetes duration of 6–10 years but thinner in those with >10 years. No correlation was found between CCT and duration of diabetes.

DISCUSSION

The diabetic cornea is characterised by morphological and functional changes that can affect the cornea endothelial function, which can lead to an increase in the CCT.^[9,11] CCT is an important tool used to assess the metabolic status of the cornea and its endothelial pump, especially in poor-resource areas, where specular microscopy is not available. In this study, the CCT was evaluated and compared between diabetic and non-diabetic participants, which showed that there was no significant difference (p = 0.572) in the CCT measurements found between the diabetic participants (520.74 ± 48.8 um) and the non-diabetic group (524.62 ± 28.7 um). These findings were similar to studies carried out by Inoue et al,^[14] who evaluated the endothelial cell density in 99 patients with type 2 DM, which even though was decreased, CCT measurements were similar in both groups. Diabetic patients were also grouped according to their stage of diabetic retinopathy, but CCT findings were similar regardless of the severity of diabetic retinopathy.

However, these values were contrary to the findings observed by Mathebula and Segoati^[15] in South Africa, where higher CCT values (567.14 + 14.63 µm) were observed in people with diabetes as compared to the non-diabetic group (531.14 + 43.4 µm). Furthermore, Storr-Paulsen et al.,^[9] in a study carried out comparing the corneal endothelial morphology and CCT between participants with type 2 DM and non-diabetic controls, found thicker CCT in the diabetic group but did not show any significant difference in the endothelial cell density and morphology between the two groups.

In this study, the mean CCT in subjects with diabetes of duration between 6 and 10 years was higher (531.19 ± 12.1 µm) than that of those who had been diagnosed for <5 years (518 ± 56.9 µm). However, CCT findings were also noticed to be thinner (518.38 ± 51.5 µm) in study participants with diabetes duration >10 years [Table 4]. Studies carried out by Lee et al.,^[16] revealed that patients with a diabetic duration of over 10 years had more corneal morphological abnormalities compared with the normal subjects, and CCT was found to correlate significantly with diabetic duration after controlling for age. Furthermore, Sreckovic et al.^[17] found higher CCT measurements in diabetic participants with a diabetes duration of more than 15 years. The average CCT measured for males and females were 520.6 + 46.9µm and 519.4 + 49.9µm respectively, however intra-ocular pressure was noticed to be higher in females (19.6 +4.9mmHg) than males (15.2 + 3.0mmHg ) [Table 5].

When CCT was compared with HbA1c levels, CCT was noticed to be slightly higher in study participants with HbA1c levels >6.5% (521.57 ± 45.2 µm) than participants with HbA1c <6.5% (519.75 ± 53.6 µm), but these values were not statistically significant (p = 0.881). A study by Pandey et al.^[11] showed significantly higher CCT measurements (540.01 µm) in patients with poor glycaemic control than in study participants with good control (522.46 µm). In contrast, Storr-Paulsen et al.^[9] correlated glycaemic status by taking an average of 4 HbA1c tests with an interval of 3 months as a reflection of long-term glycaemic status and found that HbA1c had no impact on CCT. El-Agamy and Alsubaie^[18] examined 57 patients with type 2 DM and divided them into Group 1 (patients with HbA1c <7.5%) and Group 2 (HbA1c > 7.5%) also found no significant correlation between their CCT and HbA1c levels.

An interesting finding in this study was that a higher IOP was significantly associated with the diabetic study group (18.42 ± 4.9 mmHg) than in the non-diabetic participants (16.82 ± 3.9mmhg), but no significant correlation between duration of diabetes and IOP. Results from Sreckovic et al,^[17] also showed similar findings of higher IOP in diabetic participants, with the highest IOP values recorded in patients with DM >15 years.

CONCLUSION

This study found no significant difference in CCT between diabetics and non-diabetics, nor a correlation with diabetes duration or HbA1c levels.