ACTA 0 P H T H A L M O LOG ICA 71 (1993) 169-172

Correlation of corneal thickness with blood glucose control in diabetes mellitus

L. Pierro, R. Brancato and E. Zaganelli

Department of Ophthalmology, Scientific Institute, H. S. Raffaele, University of Milano, Italy

Abstract. The aim of this study was to prove the exis- tence of a correlation between corneal thickness and gly- caemic control in insulin-dependent patients. Ultra- sound pachometry and blood glucose measurements were taken in 87 patients three times a day: fasting, two, and four hours after lunch. The sample was divided into three groups of patients: 30 of them did not have retino- pathy, 30 presented background retinopathy and 27 pro- liferative retinopathy. Thirty normal age-matched sub- jects were the control group. No correlation was found between pachometry values, blood glucose and duration of diabetes in the three groups (p > 0.05). A significant in- crease in corneal thickness was found in patients with background and proliferative retinopathy compared to the others (p < 0.01). No corneal thickness differences re- sulted between background and proliferative reinopathy (p = 0.74).

Key words: ultrasound pachometry - corneal thickness - diabetes mellitus - glycaemia.

Increased corneal thickness in insulin-dependent diabetic patients with proliferative retinopathy has already been demonstrated (Busted et al. 1981). No data on the correlation between corneal thickness and glycaemic control in these patients have been reported.

The aim of this study was to investigate this correlation.

Subjects and Methods

A total of 87 insulin-dependent diabetic patients (52 males, 35 females) were selected from the medi-

cal and eye clinics. Exclusion criteria were as fol- lows:

- previous eye surgery - corneal lenses - ocular hypertension - pregnancy or estro-progestinic therapy - high myopia.

Blood glucose was measured (L.B.) with Dextro- stix, three times a day: fasting (08.00 a.m.) and at in- tervals of 2 and 4 hours after lunch (02.00 p.m., 04.00 p.m.). Central corneal thickness was then measured by ultrasound pachometry (Corneo Scan II Storz) with a 20 MHz probe. The operator (L. P.) took three consecutive measurements and the most frequently frozen value (SD < 0.001) was listed. Both eyes were tested.

After corneal investigation, the patients under- went a Goldmann lens ophthalmoscopic examin- ation (E.Z.).

Corneal thickness evaluation, blood glucose measurement, and the fundus examination were each performed by examiners unaware of the other’s results.

The case list was divided into three groups on the basis of retinal lesions: 1) diabetics without retinopathy (30); 2) diabetics with background retinopathy (30); 3) diabetics with proliferative retinopathy (27).

The age range of the sample group was 20-68 years, mean 37.66, SD 13.32. The mean ages of each sub-group were:

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Table 1. The corneal thickness in each group.

Patients Mean corneal thickness SD

30 Control group 30 IDDM without retinopathy 30 IDDM with background retinopathy 27 IDDM with proliferative retinopathy

0.6

0.55

0.559 f 0.017 0.570 f 0.049 0.601 f 0.041 0.604 f 0.023

. I

I I .

. : ! I ; . . . - i I I .

1) diabetics without retinopathy 31.27 f 10.58 years.

2) diabetics with background retinopathy 33.90 f 8.81 years.

3) diabetics with proliferative retinopathy 48.59 f 12.12 years. Duration of diabetes for the 87 patients from 2

months to 32 years, mean 13 years. In each sub- group the mean duration was: 1) diabetics without retinopathy 94.2 k 69.7

months.

0.65 t

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2) diabetics with background retinopathy 141.3 f 74.2 months.

3) diabetics with proliferative retinopathy 247 f 63.8 months. Control corneal thickness values were obtained

by measuring 30 normal age-matched subjects, se- lected from the out-patient eye clinic, with the same exclusion criteria (age range 20-52 years, mean 32.6 f 11.42).

Results

There was no significant difference between the sexes in any of the groups (t-test).

Two-way variance analysis showed no differen- ces in corneal thickness between the right and left eye, or at any of the three examination intervals in any of the three groups. No glycaemic changes were found in any of the three groups at any of the three intervals (one-way analysis). Therefore, the right eye at 08.00 a.m. was chosen at random for statistical testing.

The corneal thicknesses of the normal group was 0.559 f 0.017, of diabetics without retinopathy 0.570 f 0.049, of diabetics with background retino- pathy 0.061 & 0.041, and of diabetics with prolif- erative retinopathy 0.604 f 0.023 (Table 1).

Significant differences in corneal thickness were found in the background and proliferative retino- pathy groups compared to non-retinopathy group (p < 0.01, non-paired Student’s ttest) (Fig. 1).

No significant difference in corneal thickness was found between the background and prolif- -

“0,WIcll 1) U wlhout D U hokqluund D U prolot erative retinopathy groups (p = 0.74). Mean fasting wbieslr rslmopolS relmYp0lil)r Iclmup“lhy

blood glucose value was 178 f 60.77 mg/day in the group without retinopathy, 227 f 78-14 in the group with background retinopathy and 141 f 38.39 in the group with proliferative retinopathy. Mean HbAlc was 7.6 f 1.29% for the group without

Fig. 1. The significant difference in corneal thickness in the background and proliferative retinopathy groups corn- pared to non-retinopathy group (p < 0.01, non-paired

Student’s t-test).

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retinopathy, 7.6 f 1.18% for the group with back- ground retinopathy, 9.9 f 1.2% for the group with proliferative retinopathy. Mean total daily insulin dosage was 28.32 k 14.1 IU for patients without re- tinopathy, 39.5 f 9.02 IU for patients with back- ground retinopathy, and 22.0 f 3 IU for patients with proliferative retinopathy.

No correlation was found between corneal thickness and any of the following factors: age of the patients, HbAlc, total daily insulin dosage, blood glucose concentration and duration of diabetes for each group (multiple stepwise regres- sion analysis).

Discussion

Previous works on corneal thickness (Busted et al. 1981; De Cevallos 1976; Ehlers 1970; Hansen 1971; Millidot 1975) used an optical pachometer. We preferred to use ultrasound pachometry to obtain more precise results and to eliminate errors intrin- sic in operator interpretation (Villasenor 1986).

In the hypoxic conditions that may result from trauma or from any malpositioning of the corneal lenses, the epithelium metabolizes glucose an- aerobically, producing more than normal amounts of lactic acid. When this diffuses into the stroma it raises the osmolarity level, and gives rise to stromal edema (Millidot 1975; Villasenor 1986). Therefore our study expressly excluded patients with corneal lenses and those who had undergone surgery. Re- ports on the correlation between corneal thickness and IOP reach contradictory conclusions. A slight increase in corneal thickness with increasing IOP has been noted by some authors (Hansen 1971; De Cevallos 1976), and the opposite effect was found by others (Ytteborg 1965; Ehlers 1970). Thus we also excluded any patients with glaucoma.

Patients who were pregnant or were receiving estro-progestinic preparations of any type were also excluded, as they present increased corneal thickness. Hormonal changes lead to retention of water in the cornea (Weinreb 1988).

In high myopia the cornea is thinner than in normal eyes (Tokoro 1971). We excluded patients with high myopia.

We did admit patients with proliferative retino- pathy who had been treated by laser. Corneal thickness appears to be the same in patients with proliferative retinopathy who have undergone

laser treatment and those who have not (Busted 1981).

In contrast to previous studies of corneal thick- ness (Busted 1981), we found a thickening not only in patients with proliferative retinopathy but also in those with background retinopathy.

Statistically, no differences were found between the proliferative and background groups (p = 0.74). Clearly, therefore, corneal thickness increases very early in diabetes, and could be correlated to the earliest retinal lesions. This seems to confirm the parallel behaviour of corneal thickness and retinal changes.

Like the vascular endothelium, the function of the corneal endothelium is to act as a cellular bar- rier. It does this by impeding the flow of aqueous humor towards the stroma and by extracting water from it, mainly by means of the sodium-potassium metabolic pump. Fluorophotometric studies have shown increased pump activity in insulin-depend- ent patients (Lass 1985). Patients with type I diabetes also present a reduction in cell density, with loss of hexagonal cells, which are theoretically the most stable (Schultz et al. 1984). If corneal en- dothelium function is impaired, corneal hydration suffers and consequently the cornea thickens (Hedbys & Mishima 1962).

Reduction of the negative charge of endothe- lium-aqueous humor interfaces, causes in the cor- neal endothelium the same phenomenon to occur in the avascular diabetic glomerulus (Schober et al. 1982): reduction in the Na-K ATPase enzyme activ- ity, with consequent alteration of Bicarbonate out- flow (Huff & Green 1983). The lack of correlation between corneal thickness and the following fac- tors: blood glucose levels at various times of day, glycosylated hemoglobin and insulin dosage casts further doubt on the role of metabolic manage- ment in the ocular complications found in diabetes.

References

Busted N, Olsen T & Schmitz 0 (1981): Clinical observa- tions on the corneal thickness and the corneal endo- thelium in diabetes mellitus. Br J Ophthalmol65: 687- 690.

De Cevallos E, Dohlman C H & Reinart W J (1976): Cor- neal thickness in glaucoma. Ann Ophthalmol 8: 177- 182.

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Ehlers N (1970): On corneal thickness and intraocular pressure. 11. A clinical study on the thickness of the corneal stroma in glaucomatous eyes. Acta Ophthal- mol (Copenh) 4 8 1107-1112.

Hansen F K (1971): A clinical study of the normal human central thickness. Acta Ophthalmol (Copenh) 48: 82.

Hedbys B 0 & Mishima S (1962): Flow of water in the cor- neal stroma. Exp Eye Res 1: 262-275.

HuffJ W & Green K (1983): Characteristic of bicarbonate, sodium and chloride fluxes across the rabbit corneal endothelium. Exp Eye Res 3 6 607-615.

Lass J H, Spurney R V, Dutt R M, Andersson H, Kochar H, Rodman H M, Stem R C & Doershuk C F (1985): Mor- phologic and fluorophotometric analysis of the cor- neal endothelium in type I diabetes mellitus and cystic fibrosis. Am J Ophthalmol 100 783-788.

Millidot M (1975): Effect of hard contact lenses on cor- neal sensitivity and thickness. Acta Ophthalmol (Co- penh) 53: 576-584.

Schober E et al. (1982): Glycosylation of glomerular base- ment membrane in type I diabetic children. Diabetolo- gia 22: 485-487.

Schultz R 0, Peters M A, Sobocinski K, Nassif K & Schultz K J (1984): Corneal endothelial changes in type I and type II diabetes mellitus. Am J Ophthalmol 98: 403-410.

Tokoro T, Hayashi K & Muto M (1971): Central corneal thickness in high myopia. Folia Ophthalmol Jap 27 610.

Vilasenor R, Santos V R, Cox K C, Harris D F, Lynn M & Waring G 0 (1986): Comparison of ultrasonic corneal thickness measurements before and during surgery in the prospective evaluation of radial keratotomy (PERK) study. Ophthalmol 93: 327-330.

Weinreb R N, Lu A & Beeson C (1988): Maternal corneal thickness during pregnancy. Am J Ophthalmol 105:

YtteborgJ & Dohlman C H (1965): Corneal edema and in- traocular pressure. 11. Clinical results. Arch Ophthal- mol74 477.

258-260.

Received on August 20th, 1992.

Author’s address: Prof. R. Brancato, Clinica Oculistica, Universita’ di Milano, H. S. Raffaele, Via Olgettina 60, 1-20132 Milano, Italy.

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