FP754 : Correlation of Central Corneal Thickness Measurement with Glycemic Control in Diabetic Patients

Dr. Shruti Bonda, B18477, Dr. sujana inampudi, Dr. Saumendu Mohanty, Dr. Sumita Mohapatra

INTRODUCTION

Central corneal thickness is the most important clinical aid for the diagnosis of glaucoma. Various evidence have come up with the conclusion that CCT not only influences the IOP but can also predict the occurrence of glaucomatous optic neuropathy. Data from ocular hypertension has demonstrated that patients with thinner corneas is an independent risk factor for the development of primary open angle glaucoma.

Persons with diabetes are thought to be at higher risk of glaucoma. The Blue Mountains Eye Study and other studies showed that persons with diabetes are at increased risk of developing glaucoma but  the mechanism in which diabetes and hyperglycemia predispose a person to glaucoma is uncertain. One hypothesis is that  hyperglycemia may cause corneal endothelial dysfunction with resultant stromal hydration and swelling of the cornea. Indeed, abnormalities of corneal endothelial morphology such as polymorphism, polymegatheism, decrease in percentage of hexagonal cells, higher coefficient of variation, and increased CCT have been detected on specular microscopy in persons with diabetes. Older diabetics also demonstrated a significant decrease in cell density in the fourth and fifth decades compared with age-matched controls. Thus  hyperglycemia influences corneal thickness and IOP measurements. However,there have been  few studies that have directly examined the relationship of diabetes and hyperglycemia with CCT

In a small clinic-based study (n -81), persons with diabetes had thicker central corneas than persons without diabetes. In addition, those with proliferative retinopathy (n -23) had greater CCT values than those without proliferative retinopathy. Another study described differences of corneal thickness and corneal endothelial morphology in patients with diabetes as compared with age-matched healthy controls. In that study of 200 persons with diabetes and 100 controls, those with diabetes were found to have thicker corneas. Data from a randomized clinical trial, the European Glaucoma Prevention Study, showed that participants with diabetes had thicker central corneas than persons without diabetes.

Corneal abnormalities that occur in diabetes mellitus( DM ) are termed as diabetic keratopathy. Several clinical studies have shown that patients with diabetes have abnormalities such as higher corneal autofluorescence, lower corneal sensitivity,  greater corneal thickness, less endothelial density.

Corneal endothelium plays a major role in maintaining the optical transparency of the cornea. These cells have limited mitotic capacity and chronic metabolic changes on the cellular level seems to affect the monolayer of corneal endothelial cells.

We have not seen any previous study comparing CCT before and after treatment of the same diabetic patients. The purpose of this study was to evaluate CCT in diabetic patients with poor glycemic control and whether there will be a significant change in these measurements after successful control of hyperglycemia.

MATERIALS & METHODS:

A clinical prospective study, including 65 patients with type II diabetes mellitus whose serum HbA1c levels were above 7% , was performed. An informed consent was obtained from all patients. The study protocol was approved by the institution’s ethics committee.

Ophthalmic examination including medical history, biomicroscopic examination of anterior segment, dilated fundus examination with 90D lens were performed. Any patients having history of ocular disease, previous ophthalmic surgery, using topical ocular medications and wearing contact lenses were exluded from study. Age and sex of patients, and duration of DM were recorded.

Corneal thickness was determined with ultrasound pachymeter. Measurements were taken from both eyes during morning hours. Each CCT measurement was the mean of 3 pachymeter readings. Measurements were completed on each eye and these were averaged to provide a single value. Before doing this, we made a Pearson correlation test to show the correlation between the measurements of both eyes.

Then the patients were treated by the endocrinology clinic. The follow-up of patients was done by different physicians at the endocrinology clinic. After mean follow-up of 6mo (4-8mo) when glycemic control was achieved (HbA1c ≤ 7% , euglycemic status), CCT measurements were recorded again. HbA1c and CCT before and after treatments were compared. Also association between CCT and sex, duration of DM, and treatment modalities were studied.

Statistical analysis were performed by paired t test, independent samples t test, and P values 0. 05 or less were considered statistically significant. Values are shown as mean±SD.

RESULTS: There were 65 patients with type II DM having poor glycemic control (HBA1c ≥7%). Mean age of patients was 58.75(46-73) . There were 36 males and 29 females patients. Duration of diabetes was more than 10 years in 40 patients(61.5%).

Antidiabetic treatment consisted of insulin in 30(46.2%)   and oral hypoglycemic drugs in 35(53.8%)

At the beginning before treatment mean HBA1c levels was 9.36±1.79% and after achieving glycemic control by treatment mean HBA1c levels was 6.45±0.70%.

Pearson correlation was 0. 88 between the CCT of the right eye and CCT of the left eye. This value showed that CCT measurement of any eye could be used. So we used the single average value. Mean CCT before treatment ( hyperglycemic status) was 552.30±29.26µm with range of 504-604µm and after diabetic treatment (euglycemic status) was 542.36±27.20µm with range of 495-596µm. The difference was statistically significant (P =0.0001, paired t test). No statistically significant difference was found in terms of gender, duration of DM and antidiabetic treatment modalities(P =0. 53; P =0. 34; P =0. 54 respectively).

Comparison of mean HBA1c values & CCT before and after successful treatment of type II Diabetes mellitus

Patients (n=65)	Before treatment	After treatment	P
HBA1c values %	9.36 ±1.79	6.45±0.70	¹0.0001
CCT µm	552.30±29.26	542.36±27.20	¹0.0001

CCT- central corneal thickness.    ¹statistically significant; paired t test 

“Comparison of the patients’ mean initial and last HbA1c and CCT values by gender, duration of diabetes and treatment of diabetes”

	Number(%)	Initial HbA1c(%)	Last HbA1c(%)	p¹	Initial CCT(µm)	Last CCT(µm)	p¹
Gender
Male	36(55.4)	9.77±2.00	6.50±0.74	³0.0001	554.74±31.73	542.70±30.35	³0.0001
Female	29(44.6)	8.92±1.44	6.39±0.68	³0.0001	549.68±26.74	542.00±23.97	³0.0001
p²		0.08	0.57		0.53	0.92
Diabetes duration
<10a	25(38.5)	10.03±2.27	6.67±0.69	³0.0001	547.40±26.69	536.45±24.73	³0.0001
≥10a	40(61.5)	8.94±1.28	6.30±0.68	³0.0001	555.37±30.77	546.06±28.39	³0.0001
p²		³0.03	0.07		0.34	0.21
Diabetes therapy
Insulin	30(46.2)	10.04±1.91	6.58±0.73	³0.0001	549.58±29.12	538.12±27.08	³0.0001
Oral drugs	35(53.8)	8.77±1.48	6.33±0.67	³0.0001	554.64±29.71	546.00±27.27	³0.0001
p²		³0.01	0.19		0.54	0.30

 P¹: Comparison between initial and last measurements was made by paired-t test

 P²: Comparison between initial-initial and last-last measurements was made by independent samples t test

³statistically significant difference

DISCUSSION:

Various types of corneal disorders, termed diabetic keratopathy, are common in persons with DM. Reduced tear production, decreased corneal sensitivity, and changes in endothelial morphology and function, alterations of corneal epithelial basement membrane and increased corneal thickness have been documented in diabetic patients.

CCT changes associated with DM have been reported in various studies.

Lee et al measured CCT of diabetic patients and found higher CCT values in patients with DM compared with control group. They also found that CCT was thicker in patients with diabetes of over 10 years. These changes may be associated with blood glucose concentrations[11] . We have found a slight increase in CCT of our diabetic patients with more than 10 years’ duration when compared to less than 10 years’ duration, but it was not statistically significant.

Unlike previous studies which comparing CCT in diabetic patients and in control groups, we assessed the change in CCT measurements in the same diabetic patient group before and after achieving a good glycemic control.

The results of our study showed that mean CCT was thicker in hyperglcemic condition than euglycemic condition in the same patients.

In our study, we did not find a significant difference in CCT in relation to the duration of diabetes, although the mean CCT was thicker in patients with diabetes of over 10 years. Interestingly, mean initial HbA1c level of patients with diabetes of over 10 years was less than the patients with diabetes of shorter duration. This finding may be explained by shorter life span of erythrocytes due to chronic metabolic disease. As a result, young red blood cells which are devoid of glucose accumulation enter into the circulation and lower HbA1c concentration.

Choo et al found that endothelial cell density in diabetic group was significantly less than that in control group, and CCT was higher in diabetic patients although it was not significant. Also they found that duration of DM and HbA1c levels were not significantly correlated with corneal endothelial findings.

Storr-Paulsen et al showed a significant increase in CCT in type 2 diabetic group (538 vs 546µm) and no correlation with HbA1c level. They also found that in diabetic group, lower endothelial cell count were associated with higher HbA1c values (P≤0. 05).

Ozdamar et al found significantly greater CCT measurements in diabetic eyes compared with control eyes. The mean CCT was greater in eyes with proliferative diabetic retinopathy (PDR) compared with those with non proliferative diabetic retinopathy and no diabetic retinopathy, but difference was not statistically significant. This may be explained as patients developing PDR, evidently have bad glycemic control.

Su and co-workers examined the relationship of diabetes and hyperglycemia with CCT and demonstrated mean CCT was6.5µm thicker in diabetic patients than in persons without diabetes. And this difference was significant (P≤0.001) . There are some studies investigating the effects of glycemic control on refraction in diabetic patients. Huntjens et al , and Li et al , showed that short term variation in CCT was similar in control subjects and the diabetic patients. There was no significant difference between groups, even though the diabetic corneas were thicker compared to controls. This suggests that short term changes in blood glucose levels do not have a significant effect on CCT in diabetic patients.

In our study we found a correlation between corneal thickness and the higher HbA1c values. HbA1c reflects the mean blood glucose level during the preceding 6 to 8wk, it reflects the patients’ general tendency to diabetes control.

We found that CCT decreased significantly with the change from hyperglycemic status to euglycemic status as reflected by the measurements of HbA1c, in our diabetic patients. We think that this finding will be useful in clinical practice in the evaluation of IOP measurements of diabetic patients.

Patients with type 2 DM have an increased risk of developing open angle glaucoma. Diabetes affects corneal biomechanics, this results in lower corneal hysteresis values than those in healthy control subjects . This may cause high intraocular pressure ( IOP ) measurements. Goldman applanation tonometry ( GAT) estimates IOP by measuring the force required to flatten an area of cornea, so corneal characteristics including its thickness can affect IOP measurements. Thicker central corneas may lead to overestimation of the real IOP in diabetic patients . Biswas et al confirmed this correlation between increasing IOP and increasing CCT as measured by GAT in diabetic patients.

It was shown that every 10µm change in CCT could yield 0.47 – 0.98mmHg deviation in IOP measurements by non contact tonometer , and 0. 28 – 0.37mmHg deviation by GAT.

In conclusion, we found that, even though mean hyperglycemic and euglycemic CCT measurements were in normal range, CCT decreases significantly by lowering HbA1c level (good glycemic control). So Glycemic status (HbA1c) should be considered when examining the eye of diabetic patients.

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