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Year : 2019  |  Volume : 12  |  Issue : 3  |  Page : 186-190  

Corneal thickness and endothelial cell density in children with type 1 diabetes mellitus

Department of Ophthalmology, Bharati Vidyapeeth (Deemed to be University) Medical College, Pune, Maharashtra, India

Date of Web Publication11-Oct-2019

Correspondence Address:
Dr. Shubha Nagpal
Department of Ophthalmology, Bharati Vidyapeeth (Deemed to be University) Medical College, Pune, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ojo.OJO_21_2018

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BACKGROUND: The aim of this study was to detect the effect of diabetes on the corneal endothelium in patients of Type 1 diabetes in the pediatric age group and to compare them with age-matched controls. Further, it was proposed to establish any correlation between these changes and risk factors of diabetes, viz., age, duration of diabetes, and hemoglobin A1c (HbA1c) values.
MATERIALS AND METHODS: This was a prospective cross-sectional study. Fifty children with Type 1 diabetes, between the ages of 7 and 17 years (average, 12.16 ± 2.63 years), and fifty healthy age-matched controls (average 12.28- ±3.00 years) were examined. The central corneal thickness (CCT) and endothelial cell density (CD) were assessed by the Topcon SP-1P specular microscope. The duration of diabetes (average, 3.91 ± 1.65 years) and the HbA1c values (average, 10.92 ± 2.28) were also noted.
RESULTS: The average CCT in the diabetics was 525.16 ± 33.14 μ and in the controls 513.44 ± 29.46 μ. This was significantly higher (P = 0.015). The average endothelial CD in the diabetics was 3039.64 ± 292.84 cells/mm2 and in the nondiabetics 3360.41 ± 268.04 cells/mm2. This was significantly lower (P < 0.001). A significant correlation was found between the endothelial CD and age of the diabetic patients (P = 0.008). However, there was no significant correlation between the endothelial CD and the CCT with either duration of diabetes or HbA1c.
CONCLUSIONS: A significant decrease in the endothelial CD and increase in the CCT occurs in children and adolescents with Type 1 diabetes. With the age of the diabetic patients, the endothelial CD significantly reduces. However, duration of diabetes and HbA1c do not affect these values.

Keywords: Central corneal thickness, endothelial cell density, type 1 diabetes mellitus

How to cite this article:
Fernandes SI, Nagpal S. Corneal thickness and endothelial cell density in children with type 1 diabetes mellitus. Oman J Ophthalmol 2019;12:186-90

How to cite this URL:
Fernandes SI, Nagpal S. Corneal thickness and endothelial cell density in children with type 1 diabetes mellitus. Oman J Ophthalmol [serial online] 2019 [cited 2022 Dec 10];12:186-90. Available from: https://www.ojoonline.org/text.asp?2019/12/3/186/268915

   Introduction Top

Diabetes mellitus (DM) is a systemic disease that alters the major metabolic pathway in the human body, affecting all organ systems. Type 1 DM (TIDM) probably accounts for 5%–10% of all diagnosed diabetes. About 50%–60% of patients with TIDM are diagnosed before 20 years of age. Hence, diabetes can be considered as one of the most common chronic diseases of childhood.[1] India accounts for most of the children with TIDM in Southeast Asia.[2] As per the sixth edition of the International Diabetes Federation diabetes  Atlas More Details, three new cases of T1DM/100,000 children of the 0–14 years age group are detected in India each year.[3]

Maintaining a healthy and transparent corneal stroma is the primary physiological function of the corneal endothelium. The endothelium also secretes a collagen matrix that forms the Descemet's membrane.[4] A low endothelial count can lead to impairment of the endothelial pump resulting in corneal hydration and subsequent decompensation.

Cataracts are known to be more prevalent in diabetics.[5],[6] Studies on the corneal endothelial density (cell density [CD]) and central corneal thickness (CCT) in adult diabetics undergoing cataract surgery have shown a higher cell loss as well as a delay in the postoperative recovery of corneal edema.[7] Similar results were also obtained by Mathew et al. after manual SICS was performed on 153 diabetic patients.[8]

Children with T1DM are likely to develop cataract and be subjected to surgery earlier than nondiabetics.[9] In view of this, the risk of dysfunction of corneal endothelium cells may affect postoperative recovery.[10]

Many studies have analyzed the corneal endothelium in adults with TIDM and Type 2 DM. These have shown that these patients have a lower mean CD with more pleomorphism and polymegathism.[11],[12],[13] However, similar studies for Type 1 diabetics of the pediatric age group are few.[12] On a literature search, no study on the Indian population of children with T1DM was found.

The aim of this prospective cross-sectional study was to detect the effect of DM on the corneal endothelium by measuring the corneal endothelial cell count and CCT in Type 1 diabetic patients of the pediatric and adolescent age group, and by comparing them with age matched controls. Further, it was also proposed to establish any correlation between the endothelial changes and the duration of diabetes, hemoglobin A1c (HbA1c) values, and age of the patient.

Early detection of corneal dysfunction in such cases will lead to early prevention of the sequelae. This is especially significant for juvenile diabetics who may be subjected to cataract surgery at a relatively early age.

   Materials and Methods Top

The study was conducted at a tertiary care hospital in Western India.

Fifty children between the ages of 7–17 years attending the diabetic outpatient department of the department of pediatrics between January and December 2016 were enrolled for the study. Fifty age-matched children with no ocular complaints or systemic ailments were enrolled as the control group. Parental/guardian consent along with the consent of children above 12 years of age was obtained prior to enrolment. Approval of the institutional ethics committee was obtained before starting the study.

Children with a history of contact lens usage, previous ocular surgeries, myopia, and other ocular or systemic diseases other than DM were excluded from the study.

General patient information was noted including the name, age, sex, and registration number.

A detailed ophthalmological examination was carried out, which included best-corrected visual acuity, slit-lamp evaluation, fundus examination, intraocular pressure record, CCT, and endothelial cell count using the specular microscope of Topcon SP-1P.

In the diabetic group, the duration of diabetes was noted and the HbA1C levels were recorded.

Results were expressed with descriptive statistics, and Mann–Whitney U-test for comparison of the group parameters and correlation analysis were performed with SPSS statistical software 20.0 (online independent platform development software). Multiple linear regression analyses were done to determine different parameters and P < 0.05 was considered statistically significant.

   Results Top

Fifty (100 eyes) patients diagnosed with TIDM and 50 (100 eyes) healthy children of the age group of 7–17 years were enrolled in the study. Of the 50 children in the diabetic group, 24 were male and 26 were female. Of the healthy group, 28 were male and 22 were female. The mean age of the T1DM patients was 12.16 ± 2.63 years with a mean diabetic duration of 3.91 ± 1.65 years. The mean age of the controls was 12.28 ± 3.00 years.

All the patients in the diabetic as well as control groups had an unaided visual acuity of 6/6. No patient in the diabetic group was detected to have cataract or diabetic retinopathy.

In the T1DM group, the CCT values ranged from 442 to 631 μ with a mean of 525.16 ± 33.14 μ. This was significantly higher than that of the control group (P = 0.015), where the CCT values ranged from 456 to 583 μ with a mean of 513.44 ± 29.46 μ [Figure 1].
Figure 1: Central corneal thickness

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In the T1DM group, the corneal endothelial CD ranged from 2396 to 3791 cells/mm 2 with a mean of 3039.64 ± 292.84 cells/mm 2. This was significantly lower than that of the control group (P < 0.001) where the CD ranged from 2359 to 3879 cells/mm 2 with a mean of 3360.41 ± 268.04 cells/mm 2 [Figure 2].
Figure 2: Endothelial cell count

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The HbA1c values ranged from 5.8 to 15.8 with a mean of 10.9 ± 2.3. Only two patients had a value of <7.

The duration of diabetes ranged from 1 week to 9 years with a mean of 3.91 ± 1.65 years.

The risk factors of DM, viz., age of the patient, duration of DM, and HbA1c values were analyzed with multiple linear regression analyses. P < 0.05 was considered statistically significant.

There was no significant correlation of any of the risk parameters with CCT.

There was a significant negative correlation of the age of the patient with endothelial CD (P = 0.008) [Table 1] and [Table 2].
Table 1: Multiple linear regression analyses of central corneal thickness in diabetics

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Table 2: Multiple linear regression analyses of corneal endothelial density in diabetics

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However, there was no significant correlation of the age with CCT and CD in the control group [Table 3].
Table 3: Correlation of central corneal thickness and endothelial density with the age of nondiabetics

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   Discussion Top

Type 1 diabetes is a chronic illness characterized by the body's inability to produce insulin due to the autoimmune destruction of the beta cells in the pancreas. Onset most often occurs in childhood. Type 1 diabetes has 78,000 new cases diagnosed every year in young individuals (<5 years).[1] Maahs et al. reported that the incidence of T1DM increased with age in most populations, with the highest incidence observed in the 10–14-year olds.[13] In our study also, the largest number of patients (40%) belonged to the 11–13 years age group.

Corneal changes are diagnosed in nearly 70% of adult patients with diabetes (Type 1 and Type 2).[14]

In the present study, the average CD in patients with diabetes was significantly lower than that in the control group (P < 0.001). Módis et al. studied adults with Type 1 and Type 2 diabetes and also found a statistically significant decreased CD in Type I diabetics (2428 ± 219 cell/mm 2) in comparison with healthy controls (2495 ± 191 cell/mm 2).[15] However, no significant decrease was seen in patients with Type 2 diabetes.

Excessive sorbitol produced by glycolysis leads to an over hydration of the cells due to osmosis, eventually resulting in failure of endothelial pump function, which reduces CD.[16]

The difference in the average CCT in the T1DM group (525.2 ± 33.3 μ) and that of the controls (513.44 ± 29.46 μ) was also significant (P = 0.015). Similar results were obtained by Urban et al. who examined 123 eyes of Type 1 diabetic children and 124 eyes of nondiabetic children.[12] Tiutiuca measured the CCT for 100 children with Type 1 diabetes and 100 healthy children. He also concluded that diabetic children have a significantly increased CCT when compared with nondiabetic children.[17]

Possible explanations for increased corneal thickness in diabetic patients are inhibition of the corneal endothelial pump and an increased endothelial permeability, which result from the metabolic effects of diabetes. Excessive sorbitol is produced by glucose being reduced by the enzyme aldose reductase. This gets deposited in the endothelial cells, which osmotically draw in more solvent to quench the excessive solute, overhydrating the cells, resulting in swelling of the cornea.[16],[18]

Of the risk factors studied by us, we could demonstrate a significant (P = 0.008) negative correlation of the CD with the age of the diabetic patients (r = −0.106). No correlation was found in the control group. It may be surmised that TIDM is responsible for the significant reduction in CD in the diabetic group. The average HbA1c value of our patients was 10.92 ± 2.28, with only two patients having a value of <7. In the present study, we did not find any significant correlation between CD and CCT with HbA1c levels. This coincided with studies conducted on adults with Type II DM by Matsuda et al.[19] and Siribunkum et al.[20]

There was no significant correlation of CD and CCT with the duration of diabetes. A study conducted by Urban et al.,[12] analyzing the influence of local and systemic factors affecting the density of the corneal endothelium in children and adolescents with Type 1 diabetes, demonstrated a significant correlation between CD and the duration of diabetes. In our study, the mean age of the T1DM patients was 12.16 ± 2.63 years and the duration of diabetes ranged from 1 week to 9 years. However, of the 50 patients with T1DM, 35 had diabetes for <5 years. The disparity could probably be explained by the shorter average duration of diabetes in our patients (3.91 ± 1.65 years) as compared to theirs (8.02 ± 3.9 years) as well as the higher mean age in their study (15.34 ± 3.06 years).

Evaluating the condition of the corneal endothelium is important because one of the most frequent reasons of corneal endothelium cells loss is cataract surgery. The research done by Mathew et al. shows that the removal of cataract by manual small incision cataract surgery is exceptionally traumatizing for the endothelium in eyes of diabetic patients. The diabetic endothelium was found to be under greater metabolic stress and had less functional reserve after cataract surgery.[8] It can be assumed that for children suffering from diabetes, development of cataract in the future and the necessity for its surgery may be relatively early. In view of this, there is a significant increase in the risk of dysfunction of corneal endothelium cells. Hence, an evaluation of the corneal endothelium should be a part of the protocol for eye care of diabetic patients with special emphasis in the pediatric age group of Type 1 diabetics. This may be especially relevant in countries like India which are host to a large population of children suffering from diabetes.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Chawla R, Chawla A. FAQs in Diabetes. 1st ed. India: Jaypee Brothers Medical Publishers; 2016.  Back to cited text no. 1
Das AK. Type 1 diabetes in India: Overall insights. Indian J Endocrinol Metab 2015;19:S31-3.  Back to cited text no. 2
Aguiree F, Brown A, Cho NH, Dahlquist G, Dodd S, Dunning T, et al. IDF Diabetes Atlas. Switzerland: International Diabetes Federation; 2013.  Back to cited text no. 3
Bourne WM. Biology of the corneal endothelium in health and disease. Eye (Lond) 2003;17:912-8.  Back to cited text no. 4
Williams R, Van Gaal L, Lucioni C. CODE-2 Advisory Board. Assessing the impact of complications on the costs of type II diabetes. Diabetologia 2002;45:S13-7.  Back to cited text no. 5
Klein BE, Klein R, Moss SE. Incidence of cataract surgery in the wisconsin epidemiologic study of diabetic retinopathy. Am J Ophthalmol 1995;119:295-300.  Back to cited text no. 6
Morikubo S, Takamura Y, Kubo E, Tsuzuki S, Akagi Y. Corneal changes after small-incision cataract surgery in patients with diabetes mellitus. Arch Ophthalmol 2004;122:966-9.  Back to cited text no. 7
Mathew PT, David S, Thomas N. Endothelial cell loss and central corneal thickness in patients with and without diabetes after manual small incision cataract surgery. Cornea 2011;30:424-8.  Back to cited text no. 8
Schultz RO, Matsuda M, Yee RW, Edelhauser HF, Schultz KJ. Corneal endothelial changes in type I and type II diabetes mellitus. Am J Ophthalmol 1984;98:401-10.  Back to cited text no. 9
Roszkowska AM, Tringali CG, Colosi P, Squeri CA, Ferreri G. Corneal endothelium evaluation in type I and type II diabetes mellitus. Ophthalmologica 1999;213:258-61.  Back to cited text no. 10
Sudhir RR, Raman R, Sharma T. Changes in the corneal endothelial cell density and morphology in patients with type 2 diabetes mellitus: A population-based study, Sankara Nethralaya diabetic retinopathy and molecular genetics study (SN-DREAMS, report 23). Cornea 2012;31:1119-22.  Back to cited text no. 11
Urban B, Raczyńska D, Bakunowicz-Łazarczyk A, Raczyńska K, Krętowska M. Evaluation of corneal endothelium in children and adolescents with type 1 diabetes mellitus. Mediators Inflamm 2013;2013:913754.  Back to cited text no. 12
Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ. Epidemiology of type 1 diabetes. Endocrinol Metab Clin North Am 2010;39:481-97.  Back to cited text no. 13
Vieira-Potter VJ, Karamichos D, Lee DJ. Ocular complications of diabetes and therapeutic approaches. Biomed Res Int 2016;2016:3801570.  Back to cited text no. 14
Módis L Jr., Szalai E, Kertész K, Kemény-Beke A, Kettesy B, Berta A. Evaluation of the corneal endothelium in patients with diabetes mellitus type I and II. Histol Histopathol 2010;25:1531-7.  Back to cited text no. 15
Choo M, Prakash K, Samsudin A, Soong T, Ramli N, Kadir A. Corneal changes in type II diabetes mellitus in Malaysia. Int J Ophthalmol 2010;3:234-6.  Back to cited text no. 16
Tiutiuca C. Assessment of central corneal thickness in children with diabetus mellitus type I. Oftalmologia 2013;57:26-32.  Back to cited text no. 17
O'Donnell C, Efron N, Boulton AJ. A prospective study of contact lens wear in diabetes mellitus. Ophthalmic Physiol Opt 2001;21:127-38.  Back to cited text no. 18
Matsuda M, Ohguro N, Ishimoto I, Fukuda M. Relationship of corneal endothelial morphology to diabetic retinopathy, duration of diabetes and glycemic control. Jpn J Ophthalmol 1990;34:53-6.  Back to cited text no. 19
Siribunkum J, Kosrirukvongs P, Singalavanija A. Corneal abnormalities in diabetes. J Med Assoc Thai 2001;84:1075-83.  Back to cited text no. 20


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]

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