CLINICAL SCIENCE
Cumulative Effects of Smoking and Diabetes Mellitus on
Corneal Endothelial Cell Parameters
Veysel Cankurtaran, MD,* and Kemal Tekin, MD†
Purpose: To compare the corneal endothelial morphometric
properties and central corneal thickness (CCT) values in patients
with diabetes mellitus (DM) and age-matched healthy subjects and to
determine whether smoking increases the effects of DM on these
corneal parameters.
Methods: This prospective study included patients with type 2 DM
and their age-matched controls. The smoking history of all participants
was evaluated. Corneal endothelial cell properties including endothe-
lial cell density (ECD), average cell area (AVG), coefficient of
variation of cell area (CV), and percentage of hexagonal cells (HEX)
were obtained using a noncontact specular microscope. Consequently,
CCT was measured using an ultrasound pachymeter.
Results: This research analyzed 153 subjects in the DM group and
146 subjects in the control group. There were no statistically
significant differences in the age, sex, and smoking status of the
participants in 2 groups (P . 0.05). The corneal endothelial cell
measurements including ECD, AVG, CV, and HEX did not show
any statistically significant differences between these groups (P .
0.05). However, CCT of patients with DM was statistically
significantly thicker than that of the controls (P = 0.005). The
ECD values of the smokers with DM (2435 6 325 cells/mm2) were
statistically significantly lower than those of nonsmoker healthy
subjects (2559 6 279 cells/mm2 P = 0.008). However, the AVG,
CV, HEX, and CCT values of the smokers with DM were not
statistically significantly different compared with nonsmoker healthy
subjects (P . 0.05).
Conclusions: Although neither only DM nor only smoking has
a statistically significant effect on corneal endothelial morphometric
properties, coexistence of DM and smoking causes a significant
decrease in ECD.
Key Words: central corneal thickness, corneal endothelium, diabe-
tes mellitus, smoking
(Cornea 2018;00:1–6)
Received for publication May 24, 2018; revision received July 1, 2018;
accepted July 3, 2018.
From the *Department of Ophthalmology, Mustafa Kemal University, Hatay,
Turkey; and †Department of Ophthalmology, Ercis State Hospital, Van,
Turkey.
The authors have no funding or conflicts of interest to disclose.
Correspondence: Veysel Cankurtaran, MD, Department of Ophthalmology, Mustafa
Kemal University, Alahan Street No. 209, Antakya, Hatay 31135, Turkey
(e-mail: dr.veyselcankurtaran@hotmail.com).
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
Cornea  Volume 00, Number 00, Month 2018
Copyright Ó 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
D iabetes mellitus (DM) has become a disease of epidemic
proportions and can affect both anterior and posterior
ocular structures of the eye.1,2 As the prevalence of type 2
DM increases, concomitant microvascular complications are
also increasing.3 Diabetic retinopathy (DR) is still one of the
leading causes of blindness even in developed countries that
affects approximately 4.2 million people worldwide.1 In
addition to DR, patients with diabetes are at a greater risk
of corneal endothelial damage, keratoepitheliopathy in the
form of recurrent corneal erosions, persistent epithelial
defects, reduced corneal sensitivity, and superficial kerati-
tis.1,2,4,5 A variety of studies have investigated the morpho-
logical and physiological alterations in the corneal
endothelium of patients with DM and documented several
abnormalities such as increased central corneal thickness
(CCT), decreased endothelial cell density (ECD), and
increased polymegathism and/or pleomorphism.5–9
Smoking is another important factor related to many
ocular diseases such as age-related macular degeneration,
glaucoma, cataract, Graves ophthalmopathy, ocular inflam-
mation, and contact lens–associated keratitis.10–12 Smoking
enhances the generation of free radicals and decreases the
level of antioxidants in the blood, aqueous humor, and ocular
tissues.13 It was documented that smoking can affect the
ocular surface and corneal endothelium.14,15 Experimental
studies also demonstrated that tobacco smoke and/or nicotine
derivatives induce apoptosis in endothelial cell cultures.16,17
Corneal endothelium is a thin monolayer, which is
formed by hexagonal cells. These hexagonal cells cover the
posterior surface of Descemet membrane and face the anterior
chamber of the eye.18 Anatomical and functional integrity of
the endothelial cells might be destroyed by several factors such
as corneal trauma, dystrophy, degeneration, or infection, which
may cause loss of corneal transparency. Corneal ECD and
morphology can be assessed using a specular microscope (SM),
which is a reliable and reproducible noncontact instrument.19,20
The aims of this study were to compare the corneal
ECD and morphology as well as the CCT values in patients
with DM and age-matched healthy subjects and to determine
whether smoking increases the effects of DM on these
corneal parameters.
METHODS
This prospective and cross-sectional study was per-
formed at a university clinic. The study protocol conformed to
the tenets of the Declaration of Helsinki and was approved by
the ethics committee. Written informed consent was obtained
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Cankurtaran and Tekin Cornea  Volume 00, Number 00, Month 2018

from the participants or legal guardians before enrollment.
Totally, 299 subjects participated in the study, and only right
eyes of the subjects were analyzed.
Patients with type 2 DM (DM group) and their age-
matched controls (control group) were included. The presence
of type 2 DM had been confirmed by the endocrinology
department. The presence and stage of DR in patients with DM
were investigated using fundus photography, fundus fluores-
cein angiography, and/or optical coherence tomography by the
same clinician (V.C.). Early Treatment Diabetic Retinopathy
Study criteria were used to describe various stages of DR.21
For detailed analysis of patients with DR, the DR group was
further divided into patients with no-DR, nonproliferative DR
(NPDR), and those with proliferative DR (PDR) based on the
diagnosis by a consultant ophthalmologist. All the control
subjects were healthy without any known systemic disease and
had applied to the ophthalmology clinic for a routine ocular
examination and/or presbyopic complaints.
The exclusion criteria of the study were a history of
ocular surgery or trauma, glaucoma, uveitis, hyperopia, or
myopia more than 3.00 diopters (D), and astigmatism more
than 1.00 D, corneal diseases such as keratoconus, Fuchs
endothelial dystrophy, corneal opacities, dry eye, contact lens
wear, use of chronic topical ophthalmic medications, and
other systemic disease except DM.
The smoking history of all participants in the study was
assessed using a modified version of the questionnaire used in
the European Prospective Investigation of Cancer study.22 A
subject smoking at least 1 cigarette per day for at least 1 year,
and currently smoking, was considered an active smoker. A
subject who has never smoked more than 100 cigarettes was
considered a nonsmoker. Moreover, the duration of DM and
the most recent glycosylated hemoglobin (HbA1c) values
were recorded for patients with DM.
All subjects underwent a comprehensive ophthalmic
examination including best-corrected visual acuity testing
using the Snellen chart (20 feet), intraocular pressure measure-
ments with a pneumotonometer, slit-lamp biomicroscopy, and
fundus examination. To minimize the effect of diurnal changes
in corneal hydration, all specular microscopy measurements
were performed at the same time interval of the day (between
10 and 12 AM) and in the same environmental conditions.
Corneal endothelial measurements were performed by
the same masked technician. Three digital photographs of the
central cornea were obtained using the same noncontact SM
(Topcon SP-3000P; Topcon Corp, Tokyo, Japan) to evaluate
the corneal endothelium. Subjects were asked to look at the
central fixation target, and the auto-alignment function was
used. All corneal endothelial cells that were clearly visible on
the image were marked manually. At least 100 cells per
measurement were included in each analysis. The center
method, which is a common technique incorporated into the
SM, was used. ECD, average cell area (AVG), coefficient of
variation of cell area (CV), and percentage of hexagonal cells
(HEX) were calculated by software of the SM. The CV in the
cell size (standard deviation divided by the mean cell area)
was used as an index of the extent of variation in the cell area
(polymegethism), and the HEX in the analyzed area was used
as an index of variation in the cell shape (pleomorphism).23
Moreover, reproducibility of specular microscopy data was
assessed by the intraclass correlation coefficient (ICC), which
is a measure of consistency for a data set, in which a value of
1 represents perfect agreement and 0.8 to 0.99 represents
almost perfect agreement. The intraobserver reproducibility
assessment was performed with a smaller study sample
consisting 10 eyes of 10 patients with DM and 10 eyes of
10 healthy subjects who underwent 3 consecutive specular
microscopy measurements.
Consequently, CCT was measured using an ultrasound
pachymeter (US 4000; Nidek, Tokyo, Japan). During the
measurements, the subjects fixated on a distant target and the
pachymeter probe was placed perpendicularly and centrally to
the cornea. Three consecutive measurements were taken for
each participant and the average values were selected for
data analysis.
Statistical Analysis
An a priori power analysis using the PASS 11 calculation
(Power and Sample Size, version 11; NCSS Statistical Soft-
ware) revealed that approximately at least 60 smokers with DM
and 60 nonsmoker controls should be enrolled to reach a power
equal to at least 80% in the study. The number of participants
achievable during the study period was 60 smokers with DM
and 82 healthy nonsmokers. The data of the study were
analyzed using Statistical Package for Social Sciences (SPSS)
version 22.0 for Windows (SPSS Inc, Chicago, IL). Descriptive
data were presented as mean 6 SD, frequency distributions,

TABLE 1. Demographics and Clinical Characteristics of DM and Control Groups

DM Group (n = 153) Control Group (n = 146) P
Age (yr), mean 6 SD (min–max) 54.9 6 6.6 (39–71) 53.9 6 7.3 (36–72) 0.305*
Sex, male/female, (n/n) 76/77 71/75 0.857†
Smokers/nonsmokers, (n/n) 60/93 64/82 0.418†
IOP, mean 6 SD (min–max) 15.8 6 1.5 (10–20) 16.1 6 2.2 (10–21) 0.404*
HbA1c (%), mean 6 SD (min–max) 8.7 6 1.8 (5.7–13.4) 5.2 6 0.2 (4.3–5.6) ,0.001*
Duration of DM (yr), mean 6 SD (min–max) 11.5 6 6.3 (1–26) — —
Bold values indicate P , 0.05.
*Mann–Whitney U test.
†x2 test.
IOP, intraocular pressure.

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Cornea  Volume 00, Number 00, Month 2018 Effects of DM and Smoking on the Cornea

TABLE 2. Corneal Endothelial Cell Characteristics and Central Corneal Thickness Measurements of the DM and Control Groups
ECD AVG CV HEX CCT
Mean 6 SD Mean 6 SD Mean 6 SD Mean 6 SD Mean 6 SD
(min–max) (min–max) (min–max) (min–max) (min–max)
DM group (n = 153) 2482.7 6 325.9 (1852–3331) 403.3 6 53.9 (297–548) 35.7 6 5.6 (25.0–54.0) 53.3 6 9.4 (31–76) 534.1 6 34.2 (461–644)
Control group (n = 146) 2530.2 6 275.5 (1881–3438) 402.4 6 44.1 (317–531) 34.5 6 4.7 (25.3–54.2) 54.2 6 10.0 (30–78) 522.7 6 34.5 (436–605)
P 0.175* 0.881* 0.086† 0.409† 0.005*
Bold values indicate P , 0.05.
*Student t test.
†Mann–Whitney U test.

and percentages. The x2 test was used to analyze the categorical
variables. The normal distribution of the variables was checked
by visual (histogram and probability graphs) and analytical
methods (Kolmogorov–Smirnov/Shapiro–Wilk test). Equality
of variances was tested by the Levene test. The 1-way analysis
of variance, Welch analysis of variance, and Kruskal–Wallis
tests were used to determine whether there were any significant
differences between the 3 groups. Post hoc tests (Tukey HSD)
for pairwise comparisons were also performed. P , 0.05 was
considered statistically significant.
RESULTS
This research analyzed 299 eyes of 299 subjects: 153
(51.2%) of the subjects were in the DM group, and the
remaining 146 (48.8%) were in the control group. There were
no statistically significant differences in the age, sex, and
smoking status of the participants in the DM and control
groups (P . 0.05, for all). In the DM group, the mean
duration of the disease was 11.5 6 6.3 years, and the mean
level of HbA1c was 8.7 6 1.8%. The demographics and
clinical data of all participants are presented in Table 1.
The corneal endothelial cell characteristics and CCT
values of patients with DM and healthy subjects are
demonstrated in Table 2. There were no significant differ-
ences between these 2 groups in terms of ECD, AVG, CV,
and HEX (P . 0.05, for all). However, CCT of patients with
DM was statistically significantly thicker than that of the
control subjects (P = 0.005). Additionally, the results of the
intraobserver reproducibility for specular microscopy data
revealed an ICC of 0.96 (P , 0.001) for ECD, 0.92 for AVG
(P , 0.001), 0.88 for CV (P = 0.001), and 0.89 for HEX (P ,
0.001) in the DM group and an ICC of 0.93 (P , 0.001) for
ECD, 0.90 for AVG (P , 0.001), 0.87 for CV (P = 0.001),
and 0.88 for HEX (P , 0.001) in the control group.
Of the total 153 patients with DM in the study, 47
patients did not have any sign of DR (no-DR), 59 patients had
NPDR, and the remaining 47 had PDR. These 3 groups were
similar in terms of age, sex, smoking status, and intraocular
pressure values (P . 0.05, for all; Table 3). However, the
HbA1c values and duration of DM were statistically signif-
icantly different between the groups (P , 0.05, for all; Table
3). The demographic and clinical characteristics of patients
with different stages of DM are shown in Table 3.
As illustrated in Table 4, the corneal endothelial cell
measurements including ECD, AVG, CV, and HEX as well
as the CCT values did not show any statistically significantly
differences between patients with No-DR, NPDR, and PDR
(P . 0.05, for all).
Table 5 reveals the corneal endothelial cell character-
istics and the CCT values of patients with DM and healthy
subjects according to their smoking status. There were
statistically significant differences among 4 subgroups in
terms of ECD and CCT values (P = 0.047 and P = 0.024,
respectively). Therefore, the post hoc Tukey test with the
Bonferroni correction was performed for binary comparisons.
The Bonferroni corrections were applied for multiple com-
parisons among 6 subgroups with a resultant significance

TABLE 3. Demographics and Clinical Characteristics of Patients With Different Stages of DM

No-DR (n = 47) NPDR (n = 59) PDR (n = 47) P
Age (yr), mean 6 SD (min–max) 54.0 6 7.2 (39–69) 55.2 6 5.9 (39–71) 55.1 6 6.3 (41–68) 0.16*
Sex, male/female, (n/n) 25/22 28/31 23/24 0.836†
Smokers/nonsmokers, (n/n) 19/28 23/26 18/29 0.977†
IOP, mean 6 SD (min–max) 15.9 6 1.4 (13–19) 15.8 6 1.4 (12–18) 15.6 6 1.9 (10–20) 0.623*
HbA1c (%), mean 6 SD (min–max) 8.1 6 1.9 (5.7–12.6) 8.8 6 1.4 (6.2–12.1) 9.0 6 2.0 (5.9–13.4) 0.001*, 0.003‡, ,0.001§, 0.501¶
Duration of DM (yr), mean 6 SD (min–max) 6.5 6 4.5 (1–20) 13.4 6 5.6 (1–26) 14.1 6 5.9 (4–25) ,0.001*, ,0.001‡, ,0.001§, 0.105¶
Bold values indicate P , 0.05.
*Significance in analysis of variance (comparison among 3 groups).
†Chi-square test.
‡Significance between No-DR and NPDR groups (pairwise comparison).
§Significance between No-DR and PDR groups (pairwise comparison).
¶Significance between NPDR and PDR groups (pairwise comparison).
IOP, intraocular pressure.

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Cankurtaran and Tekin Cornea  Volume 00, Number 00, Month 2018

TABLE 4. Corneal Endothelial Cell Characteristics and Central Corneal Thickness Measurements of Patients With Different Stages
of DM
ECD AVG CV HEX CCT
Mean 6 SD (min–max) Mean 6 SD (min–max) Mean 6 SD (min–max) Mean 6 SD (min–max) Mean 6 SD (min–max)
No-DR (n = 47) 2512.8 6 325.4 (1952–3331) 396.3 6 53.4 (300–505) 35.5 6 4.9 (25.0–49.8) 54.3 6 10.2 (35–76) 536.2 6 29.9 (486–603)
NPDR (n = 59) 2485.3 6 337.6 (1852–3229) 413.1 6 58.9 (310–548) 36.1 6 6.3 (25.7–54.0) 52.7 6 8.9 (31–67) 533.7 6 36.4 (461–644)
PDR (n = 47) 2449.4 6 314.7 (1920–3300) 397.9 6 46.7 (297–497) 35.4 6 4.7 (26–48) 53.0 6 9.2 (32–70) 532.5 6 35.9 (472–598)
P 0.206* 0.200* 0.301* 0.916† 0.871*
*Significance in analysis of variance.
†Kruskal–Wallis test.
ECD: endothelial cell density; AVG: average cell area; CV: coefficient of variation of the cell area; HEX: percentage of hexagonal cells; CCT: central corneal thickness.

level of P , 0.0083 (corrected P value = 0.05/6). As shown
in Tables 6 and 7, the ECD values of the smokers with DM
were statistically significantly lower than those of nonsmoker
healthy subjects (P = 0.008). However, the AVG, CV, HEX,
and CCT values of the smokers with DM were not
statistically significantly different compared with nonsmoker
healthy subjects.
DISCUSSION
This study investigated the corneal endothelial cell
characteristics and CCT values of patients with different
stages of DM and those of healthy subjects according to their
smoking status to see how DM and/or smoking affect these
corneal parameters. The results of the study showed that
although neither only DM nor only smoking has a significant
effect on corneal endothelium, the coexistence of DM and
smoking causes a significant decrease in ECD. According to
our knowledge, this is the first study evaluating whether
smoking increases the effects of DM on corneal endothelial
cell properties.
A transparent clear cornea is essential for optimal vision
and a healthy corneal endothelium is necessary to sustain
optical transparency of the cornea.24 The corneal endothelial
active fluid pump and barrier function are some of the most
important characteristics of a healthy cornea that maintain this
corneal transparency.24,25 In addition to the natural aging
process, a variety of factors including trauma, intraocular
surgery, ocular pseudoexfoliation, corneal endothelial dystro-
phies, inflammatory ocular disorders, and glaucoma can cause
alterations in the cell count and morphology of the corneal
endothelium.23,26,27 Moreover, several systemic diseases such
as DM may also affect the corneal endothelial properties.28
Although it was postulated that reduction in the activity of the
corneal endothelial active fluid pump and the accumulation of
advanced glycation end products in DM may cause alterations
in the corneal morphology and function,2,28 several studies
reported variable results while comparing corneal parameters
of patients with DM and healthy subjects.5–9,29 Although
lower ECD and higher CV and AVG values have been
demonstrated by various authors,30,31 there are also studies
reporting increased CCT values without any differences in
corneal endothelial morphology in patients with DM com-
pared with the healthy population.32,33 Similarly, this study
showed that although CCT is significantly thicker in patients
with diabetes, corneal ECD and morphology of patients are
not significantly different from the healthy controls. Toygar
et al34 reported thicker CCT values in patients with no-DR,
NPDR, and PDR compared with control subjects, and they
found no significant effect of retinal disease severity on CCT.
Additionally, Ozdamar et al9 found that CCT of patients with
DM is significantly thicker than those without diabetes. They
also grouped their patients with diabetes according to the
stage of DR and did not find any statistically significant
differences between these subgroups in terms of CCT, similar
to our results. Thicker CCT values of diabetic corneas could
be due to increased hydration of the cornea and nonenzymatic
glycation of biologic macromolecules and lead to advanced
glycation end products, which form irreversible cross-links
with protein backbones such as collagen.9,35

TABLE 5. Comparisons of Corneal Endothelial Cell Characteristics and Central Corneal Thickness Measurements in all Groups
Control Group (n = 146) DM Group (n = 153)
Nonsmokers (n = 82) Smokers (n = 64) Nonsmokers (n = 93) Smokers (n = 60)
Mean 6 SD (min–max) Mean 6 SD (min–max) Mean 6 SD (min–max) Mean 6 SD (min–max) P
ECD 2559.1 6 279.0 (1881–3438) 2493.2 6 268.5 (1970–3015) 2513.7 6 324.7 (1880–3331) 2434.7 6 324.5 (1852–3300) 0.047*
AVG 396.5 6 43.2 (317–531) 409.8 6 44.3 (331–520) 404.1 6 53.4 (300–531) 402.1 6 55.1 (297–548) 0.305*
CV 34.2 6 4.67 (25.3–54.2) 34.8 6 4.8 (27.0–46.3) 35.8 6 5.4 (25.0–50.2) 35.5 6 5.9 (26.0–54.0) 0.222†
HEX 54.8 6 10.5 (30.0–76.0) 53.3 6 9.4 (32.0–78.0) 53.4 6 8.7 (35.0–76.0) 53.1 6 10.2 (31.0–71.0) 0.7†
CCT 525.1 6 36.4 (436–605) 519.1 6 31.8 (457–596) 534.9 6 34.3 (461–644) 532.7 6 34.2 (465–603) 0.024*
Bold values indicate P , 0.05.
*Significance in analysis of variance.
†Kruskal–Wallis test.

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Cornea  Volume 00, Number 00, Month 2018
TABLE 6. Multiple Comparisons for ECD Among all
Subgroups
(I) Group (J) Group
ECD Smoker controls Nonsmoker controls
Nonsmoker controls Nonsmokers with DM
Nonsmoker controls Smokers with DM
Smoker controls Nonsmokers with DM
Smoker controls Smokers with DM
Nonsmokers with DM Smokers with DM
The Tukey test was used for multiple comparisons.
P , 0.0083 considered statistically significant.
In addition to cardiovascular, respiratory, and malignant
diseases, smoking has been associated many ocular dis-
eases.10–12 Chronic smoking enhances generation of free
radicals in the blood, causes oxidative damage in tissues,
increases the levels of oxygen radicals in aqueous humor, and
decreases the levels of ascorbic acid in the anterior cham-
ber.13,36 The avascular cornea may also be affected by this
oxidative damage and ischemia. Corneal endothelial cells are
also sensitive to hypoxia, and the imbalance between
oxidative and antioxidative agents might result in corneal
damage. From this perspective, limited studies have been
conducted on the effects of smoking on the corneal endothe-
lium.14,15,37–39 The variability in the results of these afore-
mentioned studies might be owing to applying different
methods and the number of participants in the studies. Similar
to the results of this study, Kara et al38 did not find any
statistically significant differences in mean CCT, mean ECD,
or parameters of endothelial cell morphology between
smokers and nonsmokers. Sayin et al14 also found no
statistically significant differences in mean CCT, mean
ECD, AVG, and CV of smokers and nonsmokers, although
a statistically significantly lower HEX was observed in
smokers than in nonsmokers. However, Ilhan et al15 detected
a statistically significant decrease in ECD values of smokers
compared with nonsmokers, whereas CCT, CV, and HEX
values were similar between the groups. In a recent study,
Golabchki et al39 revealed that the mean values of AVG and
ECD were statistically significantly different between smok-
ers and nonsmokers. The results of this study demonstrated
that only smoking did not significantly alter the corneal
TABLE 7. Multiple Comparisons for CCT Among all
Subgroups
(I) Group (J) Group
CCT Smoker controls Nonsmoker controls
Nonsmoker controls Nonsmokers with DM
Nonsmoker controls Smokers with DM
Smoker controls Nonsmokers with DM
Smoker controls Smokers with DM
Nonsmokers with DM Smokers with DM
The Tukey test was used for multiple comparisons.
P , 0.0083 considered statistically significant.
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Effects of DM and Smoking on the Cornea
endothelial cell parameters. However, coexistence of smoking
and DM caused a significant decrease in ECD. Therefore, it
could be important to inform the smokers with DM before
P ocular surgeries such as cataract or corneal transplantation.
0.092 Additionally, during the ocular surgeries on these patients,
0.296 some additional prevention such as usage of dispersive
0.008 viscoelastic devices might be considered to avoid
0.688 endothelial decompensation.
0.285 This study has several limitations. First, participants
0.12 were categorized as smokers or nonsmokers. Other categories
such as light or heavy smoking and factors such as smoking
commencement age, number of smoking years, and inhalation
patterns were not determined. Moreover, former and second-
hand smokers were not included, which limits the study.
Additionally, because of the cross-sectional nature of the
study, generalizability of the findings may be limited. The
greatest strength of our study is its large sample size, and this
is the first report to investigate whether smoking increases the
effects of DM on corneal endothelial cell properties.
To conclude, this research showed that although neither
only DM nor only smoking has a significant effect on corneal
endothelium, the coexistence of DM and smoking causes
a significant decrease in ECD. During the ocular surgeries on
patients with smokers and DM, some additional preventions
might be considered to avoid endothelial decompensation.
Further prospective comprehensive studies with histochemi-
cal investigations may help to further elucidate the cumulative
effects of smoking and DM on the corneal endothelium.
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