Original Article
Effect of Diabetes Mellitus on Central
Corneal Thickness – A Comparative Study
Qamar-ul-Islam
Pak J Ophthalmol 2017, Vol. 33, No. 3
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See end of article for authors affiliations …..……………………….. Correspondence to: Qamar-ul-Islam PNS Shifa/Bahria University Med & Dental College (BUMDC) Karachi Email: qamarulislam71@gmail.com |
Purpose: To compare central corneal thickness (CCT) of diabetes Mellitus
(DM) patientswith age matched subjects without DM and to evaluate the correlation
of CCT with glycemic status, duration of DM and severity of diabetic
retinopathy (DR). Study
Design: Cross sectional comparative study. Place
and duration of study: Eye Department, PNS Shifa
Karachi from March 2016 to February 2017. Material and Methods: Patients
with ages between 20 to 80 years of either gender who were diagnosed to have
DM were recruited in the study. Control group comprised of age matched
healthy volunteers who did not have DM. CCT was evaluated in each subject
with non-contact specular microscope (SP-3000 P, Topcon Corporation, Japan)
and all the findings were endorsed on a pre designed performa. SPSS version
13.0 was used for analysis of data. Result:
Two hundred and fifty two eyes (126 diabetic patients and 126
healthy controls) were evaluated. Both groups were age and gender matched (p >
0.05). Mean CCT of diabetic population was 512.21 ± 32.68 µm while mean CCT
of control group was 498.83 ± 28.98 µm (p = 0.001). Difference in CCT values
between subgroups of patients with no DR, with NPDR and PDR was statistically
non-significant (p = 0.810). Pearson’s correlation analysis showed that
duration of DM (r = 0.022, p = 0.809), HbA1c (r = 0.103, p = 0.251), and
severity of DR Conclusion: Significantly thicker CCT was
found in patients with DM as compared to healthy age matched controls. Key words: Specular
Microscopy, Central Corneal Thickness, Diabetes Mellitus. |
With the advent of precise and better non-invasive
measurement tools, central corneal thickness (CCT) measurement has become a
vital ocular parameter due to its importance as an indicator of corneal health
and integrity. Accurate CCT measurement (Pachymetry) has diagnostic and
therapeutic implications in various conditions like ectatic corneal dystrophies
(Keratoconus, Pellucid marginal degeneration), contact lens related problems,
dry eyes, diabetes mellitus, glaucoma and refractive surgery (LASIK)1.
For years, ultrasound pachymetry remains the gold standard method for
measurement of CCT, but newer non-invasive methods of pachymetry like
Scheimpflug system, specular microscopy, spectral domain OCT demonstrated
acceptable repeatability and reproducibility. Corneal morphological parameters
including CCT vary with age, gender, race and ethnicity. Tayyab et al and Islam
et al reported mean CCT of normal Pakistani population using specular
microscope as 503.96 µm and 505.72 µm respectively2,3.
Diabetic
keratopathy is a known entity that affects approximately 70% of diabetic
population and include decrease in corneal endothelial cell density (CED) and
hexagonality, increase in CCT, polymegethism, pleomorphism, higher corneal auto
fluorescence and lower corneal sensitivity4,5. CCT has a positive
correlation with intra ocular pressure (IOP) measured by Goldman Applanation
tonometry and this effect on measured IOP can be clinically significant6.
Thicker CCT in diabetes mellitus should be taken into consideration while
measuring IOP in diabetics. Several studies had showed variable results while
comparing CCT measurements in diabetics with normal subjects. Significantly
higher CCT values in diabetic population as compared to healthy age matched
controls had been reported by various authors4,7-9. However, there
are studies that showed no significant difference in CCT values between
diabetics and normal population5,10,11. Available data from Pakistan
on the subject is limited. This study was aimed to compare CCT between patients
with DM and non-diabetic control subjects and to analyze the correlation of CCT
in relation to diabetes duration, glycemic status and severity of DR.
MATERIALS AND METHODS
This was a cross sectional comparative
study conducted at Eye Department, PNS Shifa Naval hospital Karachi from March
2016 to February 2017. Patients with ages between 20 to 80 years of either
gender who were diagnosed to have DM were recruited in the study through non
probability convenience sampling, after approval by ethical review committee of
hospital. Written informed consent was obtained from each subject before
enrolment and study was conducted in accordance with the declaration of
Helsinki12. Sample size was found to be 126 in each group using
power of test as 80, level of significance as 0.5, mean CCT value as 566.7 µm in DR group, and 550µm in control group and
population SD as 35.77. The diagnosis of DM was based on
criteria of the American Diabetes Association (ADA) and included all the
patients who were already under treatment of physician13. Control
group comprised of age matched healthy volunteers who did not have DM (subjects
with fasting blood sugar of less than 110 mg/dL). Subjects with history of
intraocular surgery / trauma / retinal laser, corneal opacity or dystrophy,
glaucoma, pseudoexfoliation, uveitis, use of contact lens, and use of topical
eye drops were excluded. Sub groups of patients included those with no DR,
non-proliferative DR (NPDR) and with proliferative DR (PDR) on the basis of
diagnosis by a consultant ophthalmologist. Complete ocular examination
including visual acuity assessment, auto refraction, slit lamp bio microscopic
examination and non-contact IOP measurement was done in each subject. CCT was
evaluated in each subject with non-contact specular microscope (SP-3000 P,
Topcon Corporation, Japan) by a single experienced examiner between 09:00 – 11:00
AM. Three images from central cornea of eye with worse retinopathy stage in
diabetic group and randomly selected one eye in control group were captured. An
average of three readings was used for final analysis. All the findings
including demographic data, glycemic status and CCT were endorsed on a pre
designed proforma.
SPSS version 13.0 was used for analysis
of data that was tested for normality before analysis. For quantitative
variables descriptive statistics i.e. means ± standard deviation (SD) and for
qualitative variables frequencies and percentages were used. Chi square test was used to compare frequencies and percentages, while Independent
sample ‘t’ test and One way analysis of variance (ANOVA) were used to compare means ± SD between groups. Association of
CCT with DM duration, HbA1c, and severity of DR was analyzed using Pearson’s
correlation coefficient test. A p value < 0.05 was
considered statistically significant.
RESULTS
Data of 252 eyes (126 diabetic patients and 126 healthy
controls) was evaluated. Mean age of diabetic population was 54.16 ± 9.70 years
(range: 30-75 years), while mean age of control group was 52.00 ± 12.37 years
(range: 32 – 80 years). Demographic and clinical profile of both groups is
given in table 1. Both groups were matched in terms of age (p = 0.12) and gender
(p = 0.30). Mean fasting plasma glucose level was significantly higher in
diabetic group (p < 0.01). Mean CCT of diabetic population was 512.21 ±
32.68 µm (range: 403 – 623 µm), while mean CCT of control group was 498.83 ±
28.98 µm (range: 412 – 559 µm) [p = 0.001]. Patients with no DR, with NPDR and
PDR did not show statistically significant difference in mean CCT values (table
2). However, patients with no DR were significantly younger and had lower HbA1c
levels as compared to patients with NPDR and PDR (table 2). Moreover,
comparison CCT values between diabetic groups according to duration of DM
and/or HbA1c levels did not showed significant difference (table 3). Duration
of DM was significantly correlated with type of DR (r = - 0.421, p < 0.01),
HbA1c level (r = 0.175, p = 0.050), age (r = 0.305, p < 0.01) and severity
of DR (r = 0.616, p < 0.01). However, Pearson’s
Table
1: Demographic and Clinical Profile of
Study Population.
|
Parameter |
Diabetic
(n = 126) |
Control
(n = 126) |
P value |
|
Age (years) |
54.16 ± 9.70 |
52.00 ± 12.37 |
0.125 |
|
Gender Male Female |
76 (60.31%) 50 (39.68%) |
67 (53.17%) 59 (46.82%) |
0.309 |
|
Type of DM Type
1 Type
2 |
44 (34.90%) 82 (65.10%) |
- - |
- - |
|
Duration of DM <
10 years >
10 years |
60 (47.60%) 66 (52.40%) |
- - |
- - |
|
Plasma Glucose (F) mg/dL |
184.73 ± 75.90 |
97.52 ± 12.41 |
< 0.01 |
|
HbA1c Level (%) |
6.97 ± 1.12 |
- |
- |
Table
2: Clinical Profile and CCT Values
according to severity of DR.
|
Parameter |
No
DR (n = 42) |
NPDR
(n = 46) |
PDR
(n = 38) |
P
value |
|
Age (years) |
49.74 ± 10.76 |
56.80 ± 8.49 |
55.84 ± 8.24 |
0.001 |
|
Plasma Glucose (mg/dL) |
180.00 ± 83.56 |
179.76 ± 71.16 |
196.00 ± 73.33 |
0.553 |
|
HbA1c (%) |
6.51 ± 1.07 |
7.06 ± 1.23 |
7.36 ± 0.86 |
0.002 |
|
CCT (µm) mean ± SD |
512.60 ± 37.01 |
509.91 ± 28.24 |
514.55 ± 33.30 |
0.810 |
Table
3: Comparison of groups according to DM duration and HbA1c
level.
|
Parameter |
Age
(Years) |
Glucose
(mg/dL) |
CCT
(µm) |
|
Duration (years) <
10 years >
10 years p
value |
52.08 ±10.91 56.05 ± 8.08 0.021 |
181.06 ± 73.71 188.07 ± 78.25 0.607 |
513.99 ± 33.20 510.59 ± 32.38 0.563 |
|
HbA1c (%) ≤
7.5 >7.5 p
value |
53.78 ± 9.79 54.98 ± 9.57 0.522 |
158.03 ± 57.95 242.15 ± 78.68 < 0.01 |
510.98 ± 31.74 514.85 ± 34.89 0.538 |
Correlation analysis showed that duration of DM, HbA1c, and
severity of DR did not showed any significant correlation with CCT. Moreover,
plasma glucose level showed weak but significant correlation with CCT (r = 0.155,
p = 0.014).
DISCUSSION
The relationship between DM and CCT is very important as the
current burden of DM in Pakistan is approximately 7.0 million people and this
figure is expected to rise by the year 2040 to an
alarming 14.4 million making Pakistan the 8th highest country in
terms of burden of DM14. It is postulated that hyperglycemia may
cause endothelial dysfunction with resultant stromal hydration and swelling of
cornea that leads to higher CCT values in diabetic population15. Evaluation of corneal morphological
parameters including CCT has been done worldwide with conflicting reports.
Corneal morphological parameters do differ among various races and ethnic groups
with age being the major confounding factor. In this study, both groups were
age matched to eliminate the age related bias in CCT measurement among groups.
In our study, Mean CCT of diabetic population was significantly higher as
compared to normal controls (512.21 ± 32.68 µm vs. 498.83 ± 28.98; p = 0.001). Significantly
Thicker CCT values in diabetic population as compared to healthy controls had
been reported in various other studies4,7-9,15-19. Modis et al in
their study found significantly higher CCT values in type I diabetics as
compared to controls, whereas in type II diabetics the difference was not
statistically significant20. Roszkowska et alreported that
pachymetric values were significantly altered in both type 1 and type 2
diabetic groups, with values being higher in type 1 diabetics21. On
the contrary, there are studies which documented that diabetic subjects did not
differ from non-diabetic controls with regard to CCT5,10,11,22,23.
Habib et al in their study found no significant difference in pachymetry values
between diabetic and non-diabetics in Pakistani population24.
In our study, severity of DR did not
have a significant effect on CCT. Ozdamar et al 8,
Inoue et al10 and El-Agamy et al22 also reported that all diabetic groups (No
DR, NPDR and PDR) had no significant difference in pachymetry values. Whereas,
Parekh et al reported that CCT values were significantly higher in patients with moderate to severe NPDR and
PDR as compared to patients with no or mild DR23. Regarding
comparison of CCT values in patients with DM duration of ≤ 10 years and those with DM
duration of > 10 years, no statistically significant difference was
detected. Briggs et al and Habib et al reported thicker corneas in patients
with > 10 years of DM but the difference was statistically non significant18,24.
However, Lee et al and Urban et al reported significantly
higher CCT in diabetics with > 10 years of duration4,25. In our
study, comparison of the mean
values of CCT in diabetic patients with HbA1c
≤ 7.5% and those with HbA1c
> 7.5% showed no significant difference. Similar results are
quoted by El-Agamyet al22 in their work, whereas, Gupta et al19
in their study reported significantly thicker corneas in patients with HbA1c
levels of > 7.0%.
Correlation between CCT and various
systemic and ocular variables such as duration of DM, plasma glucose level,
HbA1c level and severity of DR had been extensively evaluated worldwide. In our
study, duration of DM, HbA1c, and severity of DR did not showed any significant
correlation with CCT. Non-significant correlation of duration of DM, HbA1c, and
severity of DR with corneal endothelial parameters had been found in various
studies worldwide5,7,22. However, there are studies that showed
significant correlation of CCT with duration of DM, HbA1c level and severity of
DR4,23,25
The strength of
this study was the appropriate sample size, age matched groups, and prospective
data collection. Limitations of the study include lack of multivariate
analysis, not performing gold standard test (glucose tolerance test) to exclude
diabetes in controls and not taking into account possible confounding factors
like smoking, IOP and corneal diameter. Results of this study provide a greater
insight into the understanding of corneal morphology in diabetic population
especially in the context of pre-operative evaluation and glaucoma diagnosis.
In fact, Blue Mountains eye study showed persons with diabetes are thought to be at higher risk
of glaucoma26. Therefore
it is recommended that thicker CCT associated with DM must be taken into
consideration while measuring IOP in diabetics.
CONCLUSION
Mean pachymetry values were found to be significantly
thicker in diabetic population as compared to healthy controls. However,
duration of DM, HbA1c, and severity of DR did not showed any significant
correlation with CCT.
Author’s Affiliation
Dr. Qamar-ul-Islam
Classified Eye Spec /Assoc Prof
PNS Shifa/Bahria University Med &
Dental College (BUMDC) Karachi.
Role of Author
Dr. Qamar ul Islam
Study
conception, design and interpretation of the data, the drafting of the article
or critical revision for important intellectual content.
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