Published in IJCP July 2019
Clinical Study
A Study of Corneal Thickness and Endothelial Morphology in Type 2 Diabetes Mellitus
July 12, 2019 | Rajender Singh Chauhan, Ashok Rathi, Jp Chugh, P Sharma, R Rajput, R Kumar
     


Abstract

Ocular complications of diabetes mainly include diabetic retinopathy, glaucoma, cataract and ocular surface disorders. Besides diabetic retinopathy, patients with diabetes are prone to develop corneal endothelial damage, keratoepitheliopathy in the form of recurrent corneal erosions, persistent epithelial defects and superficial keratitis. This study was conducted to assess the corneal thickness and endothelial morphology in type 2 diabetes mellitus patients and to compare these parameters with nondiabetics. The study group included 100 type 2 diabetes patients and 100 nondiabetic patients formed the control group. Specular microscopy was performed using a noncontact TOPCON SP-3000P specular microscope and SP-3000P endothelial cell analysis software (image net) on both eyes or one eye. Fasting mean blood sugar was 143.96 ± 30.83 mg/dL in study group and 77.53 ± 8.44 mg/dL in control group. Postprandial blood sugar level was also very high in study group as compared to the control group. The difference in blood sugar levels, both fasting and postprandial, between the two groups was found to be statistically significant (p < 0.001). About, 70% patients suffered from microvascular complications while both macro- and microvascular complications were observed in 35% patients in study group. Mean CCT of study group (520.09 ± 25.37 µm) was higher than mean CCT of control group (514.99 ± 21.80 µm). Statistical comparison of both the groups was found to be significant (p < 0.05). There was statistically significant lower mean hexagonality of endothelial cells, i.e., 56.69 ± 6.86% in study group, as compared to 60.79 ± 5.46% in the control group (p < 0.001). Mean ECD was slightly lower in study group (2467.27 ± 260.37 cells/mm2) as compared to control group (2498.23 ± 235.31 cells/mm2), but difference in both groups was insignificant. Difference in coefficient of variation (CV) and mean cell area was found to be insignificant in both the groups. The study concluded that the corneal health of patients with uncontrolled and long-standing diabetes is poor and can lead to loss of transparency.

Keywords: Diabetes mellitus, corneal thickness, endothelial morphology

Diabetes mellitus is a widely spread and one amongst the most common noncommunicable disease. As of 2017, 72.9 million Indians were affected by type 2 diabetes. Ocular complications of diabetes mainly include diabetic retinopathy, glaucoma, cataract and ocular surface disorders. In addition to diabetic retinopathy, diabetes patients can likely develop corneal endothelial damage, keratoepitheliopathy as recurrent corneal erosions, persistent epithelial defects and superficial keratitis. Therefore, in the presence of diabetes, it is important to weigh keratopathy as a potential sight-threatening condition and appropriate clinical attention and increased research interest should be addressed towards this condition. In the developed world and increasingly elsewhere, type 2 diabetes is the major cause of nontraumatic blindness and renal failure.

Cornea has 6 layers which are epithelium, Bowman’s layer, stroma, Dua’s layer, Descemet’s membrane and endothelium. Endothelium is a monolayer of hexagonal cells which is rich in mitochondria. There are 5,00,000 endothelial cells per cornea and the adult density is 2500 cells/mm2 approximately. Functions of corneal endothelium include regular fluid and solute transport and maintenance of corneal optical transparency via active Na/K ATPase pump. Thickness of cornea reaches adult size by 3 years of age.

Damage or insult to corneal endothelium leads to increase in central corneal thickness and loss of transparency. Diabetic keratopathy can cause alterations in all layers of cornea especially the endothelium, like decrease in endothelial cell density (ED) and hexagonality, as well as increased polymegathism, pleomorphism and central corneal thickness. Reduced corneal ECD and swelling of the cornea are indicators of corneal dysfunction.

Corneal endothelial morphology can be measured using different instruments, including contact specular microscopes, noncontact specular microscopes (NCSM) and confocal microscopes while central corneal thickness can be assessed by various techniques such as ultrasound pachymeter (USP), Orbscan, contact specular microscopy, NCSM and Pentacam. The availability of quick, accurate, noninvasive methods of central corneal thickness (CCT) assessment is essential for the effective monitoring of corneal endothelial health. One such technique widely used is the new automated NCSM Topcon SP-3000P (Topcon Corporation, Tokyo, Japan), which captures an image of the corneal endothelium and assesses corneal thickness simultaneously.

Aims and Objectives

To study the corneal thickness and endothelial morphology in type 2 diabetes mellitus patients and to compare these parameters with nondiabetics.

Material and Methods

The present study was conducted at the Regional Institute of Ophthalmology and Dept. of Endocrinology, Pt. BD Sharma PGIMS, Rohtak, Haryana. It was a case-control study in which the study group included 100 type 2 diabetes patients and 100 nondiabetic patients formed the control group. The study was conducted to detect the effect of type 2 diabetes mellitus on corneal thickness and endothelial morphology.

Inclusion Criteria

  • Individuals of either gender, age more than 18 years, who were diagnosed to have type 2 diabetes mellitus as per American Diabetes Association (ADA) criteria, blood glucose levels ≥126 mg/dL (fasting) or blood glucose levels ≥200 mg/dL (postprandial), were included as the study population.

Control group included age- and gender-matched nondiabetic individuals.

Exclusion Criteria

  • Previous history of ocular surgery or trauma.
  • Active or previous eye infection or inflammation.
  •  
  • Previous retinal photocoagulation.
  • Contact lens wear.
  • Corneal disease due to chronic conjunctival or eyelid abnormality.
  • Regular use of any eye drops.

Patient Evaluation

Informed and written consent was taken from all patients. Detailed history regarding age, gender, any previous history of ocular trauma, surgery, usage of eye drops if any, was taken. Complete ocular examination was performed, including best corrected visual acuity, using Snellen acuity chart, anterior and posterior segment examination by slit-lamp, intraocular pressure measurement, fundus examination and specular microscopy.

Methodology

Specular microscopy was performed using a noncontact TOPCON SP-3000P specular microscope and SP-3000P endothelial cell analysis software (image net) on both eyes or one eye, considering the exclusion criteria. This instrument takes a picture of the corneal endothelium by slit light projected diagonally.

Statistical Analysis

The data was entered in Microsoft excel spreadsheet and it was analyzed using SPSS version 20.0. Student’s t-test was applied for comparison between the study group and controls. The comparison among the diabetes group was made by performing analysis of variance (ANOVA) test. Pearson correlation test was also applied. Point of statistical significance was considered if p < 0.05.

Results and Observations

Fasting mean blood sugar was 143.96 ± 30.83 mg/dL in study group as compared to 77.53 ± 8.44 mg/dL in control group. Similarly, postprandial blood sugar level was also very high in study group patients, i.e., 238.48 ± 40.21 mg/dL as compared to 112.38 ± 8.17 mg/dL in the control group. The difference in blood sugar levels, both fasting and postprandial, between the two groups was found to be statistically significant (p < 0.001). Mean glycated hemoglobin (HbA1c) in study patients was
8.07 ± 1.24 % (Table 1).

Table 1. Blood Sugar Levels in Study and Control Groups

Blood sugar (mg/dL)

Study group

Mean ± SD

Control group

Mean ± SD

Statistical significance

P

Fasting

143.96 ± 30.83

77.53 ± 8.44

0.000 (<0.001 VHS)

Postprandial

238.48 ± 40.21

112.38 ± 8.17

0.000 (<0.001 VHS)

HbA1c (%)

8.07 ± 1.24

-

-

SD = Standard deviation; VHS = Very highly significant.

A total of 70% of the patients were taking oral hypoglycemic agents (OHAs). Out of insulin dependents, 12% were only receiving insulin while the rest 18% were on both insulin and OHA.

In our study, 70% patients suffered from microvascular complications while both macro- and microvascular complications were observed in 35% patients in the study group.

Mean CCT of study group (520.09 ± 25.37 µm) was higher than mean CCT of control group (514.99 ± 21.80 µm). Statistical comparison of both the groups, i.e., study versus control group, was found to be significant (p < 0.05) (Table 2).

Table 2. Central Corneal Thickness in Study and Control Groups

Central corneal thickness

Study group (n = 100)

Mean ± SD

Control group (n = 100)

Mean ± SD

Statistical significance

CCT (µm)

520.09 ± 25.37

514.99 ± 21.80

P < 0.05 S

S = Significant.

Table 3 and Figures 1-3 show comparison of endothelial parameters between both the groups. We observed a statistically significant lower mean hexagonality of endothelial cells, i.e., 56.69 ± 6.86% in the study group as compared to 60.79 ± 5.46% in the control group (p < 0.001). Mean ECD was found to be slightly lower in the study group (2467.27 ± 260.37 cells/mm2) as compared to control group (2498.23 ± 235.31 cells/mm2), but the difference in both the groups was insignificant. Difference in coefficient of variation (CV) and mean cell area was found to be insignificant in both the groups.

Table 3. Endothelial Parameters in Study and Control Groups

Endothelial parameters

Study group (n = 100)

Mean ± SD

Control group (n = 100)

Mean ± SD

Statistical significance

Minimum cell area (µm2)

183.29 ± 35.91

183.01 ± 29.24

0.933 NS

Mean cell area (µm2)

402.65 ± 43.83

414.03 ± 43.40

0.009 NS

Coefficient of variation

0.33 ± 0.04

0.32 ± 0.05

0.201 NS

ECD (cells/mm2)

2467.27 ± 260.37

2498.23 ± 235.31

0.212 NS

Hexagonality (%)

56.69 ± 6.86

60.79 ± 5.46

<0.001 VHS

SD

134.29 ± 23.81

139.61 ± 21.83

<0.01 HS

NS = Nonsignificant; ECD = Endothelial cell density; VHS = Very highly significant; HS = Highly significant.

Figure 1. Comparison of mean hexagonality in patients of both groups (200 eyes each).

Figure 2. Comparison of mean ECD in patients of both groups (200 eyes each).

Figure 3. Comparison of mean of minimum cell area and mean cell area of in patients of both groups (200 eyes each).

Discussion

In our study, mean CCT of 100 diabetes patients of study group was 520.09 ± 25.37 µm and that of 100 age- and gender-matched nondiabetics as controls was 514.99 ± 21.80 µm. The mean CCT was higher in diabetes patients when compared with the non-diabetics. It is well-known that diabetes reduces the activity of Na+/K+ ATPase of the corneal endothelium and thus, causes morphological and functional changes of diabetic cornea. The difference between the two groups was statistically significant (p < 0.05). This was in accordance with the results from other studies. In our study, we found out that mean ECD in patients of the study group was 2467.27 ± 260.37 cells/mm2 and 2498.23 ± 235.31 cells/mm2 in the control group. The ECD was lower in the study group when compared with the age- and gender-matched nondiabetic controls. The difference in cell loss was not statistically significant in our study (p > 0.05). This was in accordance with other reports. In our study, percentage of hexagonal cells was observed as 56.69 ± 6.86% in the study group and 60.79 ± 5.46% in the control group. The hexagonal shape of endothelial cells was found to be lower in type 2 diabetes patients. This difference was statistically significant as compared to the controls (p < 0.001). Similar decrease in percentage of hexagonal cells was observed in various studies done by Schultz et al and Lee et al.  In our study, mean CV in diabetes study group was 0.33 ± 0.04 as compared to 0.32 ± 0.05 of the control group. This increase in the cell size variation coefficient in type 2 diabetes patients was not significant (p > 0.05). Similar nonsignificant CV changes were observed between diabetes patients and controls in others studies.

Conclusion

The study concluded that the corneal health of patients with uncontrolled and long-standing diabetes is poor and can lead to loss of transparency. Hence, it is recommended to have strict glycemic control of type 2 diabetes mellitus for better corneal health.

Suggested Reading

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