Optometry - Journal of the American Optometric Association
Volume 80, Issue 8 , Pages 442-446, August 2009

Profile of central corneal thickness in diabetics with and without dry eye in a Saudi population

  • O. Matthew Oriowo, Ph.D., BScOptom, M.Sc.

      Affiliations

    • Corresponding Author InformationCorresponding author: O. Matthew Oriowo, Ph.D., BScOptom, M.Sc., Department of Optometry, College of Applied Medical Sciences, King Saud University, P. O. Box 10219, Riyadh 11433, Saudi Arabia.

Department of Optometry, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia

Article Outline

Abstract 

Purpose

The aim of this study was to determine the impact of diabetes in patients with and without dry eyes (DE) on central corneal thickness (CCT) measurements.

Methods

Eighty-six subjects (51 diabetics and 35 controls) participated in the study. Ultrasound pachymetry was used to measure the CCT, whereas tear break-up time (TBUT) and Schirmer tests were conducted for tear assessments. The participants were divided into group 1 (diabetics without DE), group 2 (diabetics with DE), and group 3 (nondiabetics controls). The measurements were compared using analysis of variance.

Results

The mean (95% confidence interval [CI]) of CCT was 610 (599 to 620), 601 (582 to 618), and 583 (576 to 589) μm, respectively, in diabetics without DE, with DE, and the control groups. There was significant difference in mean CCT between diabetics without DE and controls (P < 0.0001), but no significant difference in diabetics with DE versus controls (P > 0.05). The mean (95% CI) values for TBUT and Schirmer tests were 14 (13 to 15), 6 (4 to 6), 14 (14 to 15) seconds, and 21 (19 to 23), 7 (6 to 8), and 20 (19 to 21) mm, respectively, for diabetics without DE, with DE, and the nondiabetic groups.

Conclusions

DE affects the CCT in diabetic subjects, having a predilection for lower values in those exhibiting DE. In addition, the results also support the view that diabetics tend to present with higher CCT values when compared with nondiabetic patients.

Keywords: Central corneal thickness, Ultrasound pachymetry, Diabetics, Dry eye, Tear break-up time, Schirmer tear test

 

Corneal thickness considerations have become more important in eye care with the advent and advancement of different refractive surgery techniques. As well, evaluation of corneal thickness is essential in a wide range of ocular disorders such as glaucoma,1, 2 contact lens (CL) wear and related complications,3, 4 corneal ectasia such as keratoconus and keratoglobus,5, 6 dry eye (DE),7 and diabetes mellitus.8, 9

Increased corneal thickness has been reported in diabetic patients8, 9; however, the cause of the increased central corneal thickness (CCT) is still unclear. Also, it has not been shown if corneal thickness of diabetics without DE is significantly different from that of diabetics with DE. A possible question would be why is CCT measurement in diabetics with or without DE important? The importance is supported by information in the literature showing the recent guidelines established by the American Academy of Ophthalmology, in which CCT was recommended and rated higher than other ocular parameters as part of the initial examination for suspected primary open-angle glaucoma.10 The relevance of CCT is based on the fact that it is a risk factor, as it can affect the accuracy of intraocular pressure (IOP) measurement by applanation tonometry techniques.11 For instance, when an individual cornea's thickness is affected in any way, such as having abnormal rigidity or hydration, then IOP measurements will become less accurate or reliable. An abnormal corneal thickness would lead to an artifactual IOP reading; for example, a high CCT might lead to an overdiagnosis of glaucoma, whereas a low CCT may lead to an underdiagnosis.11, 12, 13 It is likely that the underestimation of IOP because of a thin cornea may delay the decision to examine visual fields and hence has the potential to delay diagnosis and treatment of glaucoma.

The maintenance of corneal thickness depends on an intact barrier function and healthy endothelium. Therefore, investigation of corneal thickness provides clinically useful information regarding corneal health and can be used as a diagnostic parameter for some eye diseases such as glaucoma and diabetes. DE in diabetics is known to be the result of decreased corneal sensation or relative numbness of the ocular surface. It is known that a common cause of DE is tear film deficiency resulting from progressive degeneration of the lacrimal glands.14 Approximately 11 million people in the United States alone are believed to be affected by DE.7 Patients with DE typically report symptoms including dryness, burning, foreign body sensation, and photophobia.

Diabetes mellitus is a very common disease worldwide, having a significant health impact on society. This is not only because of its high prevalence but also because of its chronic complications and high mortality rate,15, 16 affecting approximately 180 million people around the world.16 In India, diabetes (type I and II) is found in 13% of patients over 60 years of age,17 whereas in Spain, diabetes prevails in 10.3% of patients between 30 and 89 years.15 Despite the prevalence of DE among diabetics, there is a dearth of information on the impact of DE on the diabetic cornea. Therefore, the purpose of this study was to investigate cornea thickness in diabetics for the purpose of diabetic eye care management by comparing central corneal thickness in diabetics with and without DE.

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Subjects and methods 

This study involved 86 (51 diabetics and 35 nondiabetic) participants. The hospital setting for this study was King Fahd National Guard Hospital, Riyadh, Saudi Arabia. Subsequent to the hospital approval, diabetic patients' data were obtained by reviewing the clinical records from the hospital. The chart review process yielded 225 potential subjects as diabetic patients meeting the inclusion criteria as stated below. However, only 51 diabetics agreed to participate in the study. Diabetic subjects were the patients who had type 1 diabetes and were insulin dependent for at least 5 years before the current study. Duration of diabetes ranged from 5 to 22 years. One common diabetes type 1 therapy among the subjects was regular (short acting) soluble insulin (e.g., Actrapid® HM; Novo Nordisk A/S, Bagsvaerd, Denmark), and in some patients often combined with intermediate-acting suspension insulin (e.g., Insulatard® HM; Novo Nordisk A/S). The nondiabetic control subjects were recruited from among the patients presenting for routine eye examination with no history of contact lens wear, no complaints of ocular irritation, and no anterior segment abnormality on slit lamp biomicroscopic examination. The study protocol was approved by the King Saud University College of Applied Medical Sciences research review committee. The research was conducted in accordance with the World Medical Association' s Helsinki Declaration, and informed consent was obtained from all participants. The study participants were divided into 3 groups: group 1 (diabetics without DE, number of eyes n = 28), group 2 (diabetics with DE, n = 23), and group 3 (35 nondiabetic and non–contact lens–wearing subjects as controls, n = 35), all in the same age range.

Patients were excluded from the study if they had undergone intraocular or corneal surgery if or there was clinical evidence of rheumatoid arthritis, glaucoma, or corneal degenerative disease, such as keratoconus, corneal dystrophies, guttate, corneal scarring, or systemic (collagen related) corneal disease. Additionally, patients who had worn rigid gas-permeable or soft contact lenses up to 1 month before the study were excluded.

While reviewing patients' hospital records, a potential diabetic subject was recorded as having DE if the patient hospital data contained at least 2 of the following pieces of information: Schirmer 1 test (<10 mm/5 min), tear break-up time (TBUT) (<10 sec), fluorescein staining (>grade 2), and positive report of ocular irritation as described elsewhere.18 The DE treatment being used by the diabetics with DE attending the hospital varied among patients, including one or a combination of lid blinking therapy, washing the lid margins using warm towels to encourage proper meibomian gland secretion/flow, or the use of artificial tears. For DE comparisons, all the participants in the 3 experimental groups were assessed by means of TBUT and Schirmer 1 tear tests (without anesthesia). It was suggested that the level of invasiveness of each procedure be considered in the sequence of a DE examination.18 Hence, TBUT was performed before the Schirmer tear test.

The order of measurements was TBUT first and then Schirmer 1 tear test on the first visit, followed by pachymetry measurements 1 week later. For TBUT, a sterile fluorescein strip (1-mg Fluoret sterile ophthalmic strip, Chauvin Pharmaceuticals, Kingston-upon-Thames, United Kingdom), was soaked with 1 drop of Blink™ artificial eye drop and was applied in the lower eyelid fornix. The subject was asked to blink 3 times and then look straight forward without blinking. The tear film was observed under cobalt-blue filtered light of the slit lamp biomicroscope, and the time between the last blink and the appearance of the first break in the tear film was recorded with a stopwatch. The average of 3 consecutive TBUTs was obtained. The subject was asked to keep blinking normally, and, 3 minutes later, a precalibrated sterile Schirmer tear filter strip (Schirmer-Plus®; GECIS, Lamotte-Beuvron, France) was placed in the lower temporal fornix in the junction of the middle and outer third of the lower lid. The subject was asked to keep both eyes closed, and 5 minutes later the number of millimeters of wetting was recorded from the strip.

The corneal thickness measurements were taken using the DGH 2000 Ultrasonic Pachymeter (DGH Technology Inc., Exton, Pennsylvania) by one examiner who was not aware of the purpose of the study (to avoid bias). The DGH 2000 Ultrasonic Pachymeter probe tip is approximately 1 mm in diameter. The pachymeter was calibrated at the beginning of each session. After the instillation of a single drop of topical anesthetic (Minims®, Oxybuprocaine Hydrochloride 0.4%; Chauvin Pharmaceuticals, Surrey, United Kingdom), the pachymeter probe was placed perpendicular to the central cornea. Proper alignment was confirmed by an audible beep produced by the instrument. For each measurement session, a minimum of 3 readings was taken and an average calculated. After the corneal thickness measurement, the patients underwent a slit lamp examination. To avoid the influence of diurnal variation, all the measurements including TBUT, Schirmer 1 test, and pachymetry, were performed in the afternoon between 1pm and 4 pm.19, 20 The pachymetry measurement took approximately 3 minutes. The measurements obtained from the right eyes of all subjects were utilized for analysis by comparing control data (n = 35) with data of diabetics without DE (n = 28) and diabetics with DE (n = 23).

For statistics, all the data from the 3 study groups were analyzed with 1-way analysis of variance (ANOVA) and regression analysis for correlations using GraphPad InStat3 for Windows XP (GraphPad Software, San Diego, California; www.graphpad.com). Statistical significance was set at P < 0.05.

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Results 

A total of 86 subjects, which included 51 type 1 diabetic patients and a group of 35 nondiabetic controls completed the study. The mean age ± SD was 53.9 ± 11.9 years (range, 25 to 72 years) in the diabetic group and 52.6 ± 10.7 years (range, 25 to 70 years) in the nondiabetic control group (P = 0.44). In terms of gender distribution of participants, the diabetic group included 35.3% men and 64.7% women, and the control group contained of 45.57% men and 51.43% women (P = 0.26). Of the diabetic subjects, there were 23 (45%) with DE, and 28 (55%) without DE. Seventeen (74%) and 6 (26%) of the 23 diabetics with DE were women and men, respectively, whereas 16 (57%) and 12 (43%) of the 28 diabetics without DE were women and men, respectively.

As shown in Table 1, the diabetic group without DE had a mean (95% confidence interval [CI]) of CCT as 610 (599 to 620) μm, whereas the diabetic group with DE had a mean CCT of 601 (95% CI, 582 to 618) μm. The mean (95% CI) of CCT for the control group was 583 (576 to 589) μm. Regarding the level of differences, the cumulative mean CCT of the diabetics without DE was greater than that of diabetics with DE by approximately 9 μm (P = 0.34). The mean CCT of diabetics with DE was slightly greater than controls by 18 μm (P = 0.07). Invariably, the mean CCT of the diabetics without DE was significantly greater than the control group by 27 μm (<0.0001).

Table 1. Mean (95% CI) of CCT by group and age for all participants and P values between groups
Mean (95% CI) of CCT (in μm)P values
Age (yr)/groupsDiabetics without DEDiabetics with DEControlDiabetics without DE vs. diabetics with DEDiabetics without DE vs. controlsDiabetics with DE vs. controls
20-40617 (590-642)577 (470-683)574 (558-589)0.270.007∗0.91
(n = 4)(n = 3)(n = 8)
41-60615 (599-629)608 (583-631)586 (576-595)0.580.002∗0.09
(n = 17)(n = 15)(n = 22)
61-80596 (573-619)594 (547-641)584 (566-602)0.920.320.59
(n = 7)(n = 5)(n = 5)
All age groups610 (599-620)601 (582-618)583 (576-589)0.34<0.0001∗0.07
(n = 28)(n = 23)(n = 35)

Note. Only data for right eye were used for analysis.

∗Difference between sample means is statistically significant.

Table 2 presents the results for the mean TBUT and the mean length (millimeters) of a Schirmer tear strip moistened for 5 minutes for the different groups. For the Schirmer test, the average readings for the diabetics with DE were lower than for diabetics without DE (P < 0.0001), and there was no statistically significant difference (P = 0.30) between the average readings for the diabetic without DE and the control subjects. Also, the mean TBUT for the diabetics with DE was significantly lower than that for diabetics without DE (P < 0.0001), and there was no statistically significant difference (P = 0.55) between the mean TBUT for the diabetics without DE and the control subjects (see Table 2).

Table 2. Cumulative mean length (mm) of Schirmer tear strip moistened in 5 minutes (Schirmer 1 tear test) and TBUT in seconds
Tear testsDiabetic without DEDiabetic with DEControl
Schirmer 1 test, mm (95% CI)21 (19-23)7 (6-8)20 (19-21)
TBUT, sec (95% CI)14 (13-15)6 (4-6)15 (14-15)

Note: For diabetics without DE versus with DE, P values are for Schirmer test (P < 0.0001) and TBU T (P < 0.0001), respectively. For diabetics without DE compared with control subjects, P values are 0.30 and 0.55 for Schirmer tear test and TBUT, respectively.

The illustrations for the correlations between CCT and tear assessment are as shown in Figure 1, Figure 2, Figure 3. Although the TBUT and Schirmer tear tests are used to assess tear production and stability, respectively, it was decided to report only the TBUT illustrations because both tests had similar results in the correlation analysis. Figure 1, Figure 2 show that CCT in both the diabetics without DE (see Figure 1) and with DE (see Figure 2) is positively related to TBUT with correlation coefficients and P values being r = 0.12 (P = 0.57), and 0.52 (P = 0.007), respectively. The P values indicate that although there is positive correlation, the slope is not significantly different from zero in the case of CCT versus TBUT in diabetics without DE (see Figure 1), but in the case of CCT versus TBUT in diabetics with DE, the slope is significantly different from zero (P = 0.007, see Figure 2). In the control group, there is no direct relationship between CCT and TBUT (r = -0.21, P = 0.23; see Figure 3).

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Discussion 

The “within diabetic” group data in the current study show that mean CCT in diabetics with DE is lower by approximately 10 μm than that of diabetics without DE; however, the difference is not significant to permit a definite judgment (see Table 1), perhaps because of the small sample size. Also, the results show that CCT in the diabetic group (without and with DE) is higher than in nondiabetic controls. This is in agreement with previous findings of Busted et al.,8 who reported that the mean CCT value for diabetic corneas is about 20 μm higher than that of nondiabetic controls. In the current study, the mean CCT for diabetic without DE is 27 μm greater than that of nondiabetic controls. It has been suggested that the increased corneal thickness in the diabetics may be caused by either an increased water content or an increased dry weight content of the cornea or combination of both.8, 9

In terms of the Schirmer 1 tear test, although there is an obvious difference between readings for the diabetic without and with DE, there is no statistically significant difference between controls and diabetics without DE (see Table 2). Similarly, the TBUT results also show no significant difference between diabetics without DE and control groups, but the difference between diabetic without and with DE was significant (see Table 2). In terms of correlations between CCT and TBUT measures, although the diabetic groups show a positive relationship (see Figure 1, Figure 2), there is no direct relationship in the nondiabetic controls (see Figure 3). As mentioned earlier, the coefficient of correlation is not significantly different from zero in the diabetics without DE (see Figure 1; r = 0.12, P = 0.57), but the CCT appears to show a considerably significant upward tendency with increasing TBUT in diabetics with DE (see Figure 2; r = 0.52, P = 0.007).

Currently, it is commonly agreed that the corneal thickness values should be measured before scheduling patients for laser in situ keratomileusis (LASIK), to ensure that the CCT is sufficient to prevent leaving the corneal bed relatively thin after treatment.21 LASIK can be used to correct residual refractive errors after cataract surgery,22 and the combined refractive surgery approach (i.e., intraocular lens implantation followed by LASIK) can be applied in diabetic patients. However, because there may be compromise in the diabetic cornea, attention should be given to CCT in diabetics with cataracts, particularly those with DE, to avoid a possible risk of postsurgical keratectasia. It is therefore recommended that diabetics undergo DE and CCT examination regularly. The current study excluded patients who had undergone intraocular surgery for increased corneal thickness as described by several investigators,23, 24, 25 as well as contact lens wearers because of variations in corneal thickness with contact lens wear as reported by some investigators.4, 26, 27, 28

Overall, the diabetic patients in the current study exhibit a significantly greater-than-average CCT than nondiabetic controls (without DE). The mean CCT in diabetics with DE is lower than in diabetics without DE. Currently, the etiology of decreased CCT in corneas with DE is still not clearly understood. To shed some light on this, further studies are needed to investigate the corneal endothelium and tear film in diabetic patients with and without DE.

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Disclaimer 

The author does not have any commercial interest in any product mentioned.

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Acknowledgment 

The author thanks all the participating subjects, Hind Alshneefi, and Dr. M. Almofaraj of the Ophthalmology Department at King Fahd National Guard Hospital, Riyadh, for their assistance. The author also acknowledges the helpful comments of Drs. K. Ogbuehi (King Saud University) and E. Bitton (University of Montreal).

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PII: S1529-1839(09)00086-4

doi:10.1016/j.optm.2008.12.008

Optometry - Journal of the American Optometric Association
Volume 80, Issue 8 , Pages 442-446, August 2009

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