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Meibomian gland dysfunction and its determinants in Iranian adults: A population-based study Hassan Hashemia, Hadith Rastadb, Mohammad Hassan Emamianc, Akbar Fotouhid,
Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran Noor Research Center for Ophthalmic Epidemiology, Noor Eye Hospital, Tehran, Iran c Ophthalmic Epidemiology Research Center, Shahroud University of Medical Sciences, Shahroud, Iran d Department of Epidemiology and Biostatics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran b
A R T I C L E I N F O
A B S T R A C T
Keywords: Meibomian gland dysfunction Iran Population-based study Prevalence
Purpose: To estimate the prevalence of Meibomian gland dysfunction (MGD) and determine the associated factors in the general population in Iran. Methods: This cross-sectional study is based on the data from the second phase of the Shahroud Eye Cohort Study conducted in 2014. Of the 4737 participants of the second phase, data was available for 4700 people; their mean age was 55.9 ± 6.2 years and 2768 (58.9%) were women. Diagnosis of MGD was made based on the classiﬁcation of the International Workshop on MGD as judged by the examining ophthalmologist. The prevalence of MGD was summarized as percentage and 95% conﬁdence intervals (CI), and related factors were studied through simple and multiple logistic regressions. Results: The diagnosis of MGD in at least one eye was recorded for 1235 (26.3%) participants; the prevalence of unilateral and bilateral MGD was 26.3% (95% CI: 24.5-28.1) and 26.1% (95% CI: 24.3–27.9), respectively. In the multiple logistic regression analyses, MGD signiﬁcantly correlated with pinguecula [odds ratio (OR) = 1.3, 95% CI: 1.12–1.50], hypertension (OR = 1.34, 95% CI: 1.11–1.61), high-density lipoprotein (HDL) level (OR = 0.0992, 95% CI: 0.986–0.999), diabetes mellitus (OR = 0.83, 95% CI: 0.71–0.97), and years of education (OR = 0.98, 95% CI: 0.96–0.99). Conclusions: MGD prevalence in this study was lower than the rates reported in other studies on Asian populations. Besides HDL level, MGD is associated with another ocular surface disorder, namely pinguecula, as well as certain systemic diseases such as hypertension and diabetes mellitus. These associations should be taken into consideration when diagnosing MGD.
1. Introduction Meibomian gland dysfunction (MGD) is one of the most common disorders of the eyelids which is often overlooked . The pathogenesis is not completely understood, but in general, it appears that changes in the quality and quantity of Meibomian gland secretions (Meibum) and the resulting changes in the tear lipid composition increases tear evaporation and osmolality, and hence, the ocular surface becomes more prone to many diseases [1–3]. MGD has been shown to be the leading cause of evaporative dry eye  which is commonly detected in patients with aqueous-deﬁcient dry eye . MGD, with or without inﬂammation, can cause discomfort and visual symptoms due to tear ﬁlm instability. Prolonged inﬂammation or obstruction of meibomian glands may lead to their atrophy or loss of functioning glands . It is estimated that the prevalence of MGD in the general population
is high (range: 39–50%)  and is associated with diﬀerent systemic diseases such as diabetes mellitus, hypertension, hypercholesterolemia, atopy, and atopic dermatitis [6–11]. The few population-based studies available on this topic have reported MGD prevalence in association with dry eye which ranges from 3.5% in the Salisbury Eye Evaluation Study  to 68.3% in the Beijing Eye Study in China . Some fewer studies have investigated potential risk factors related to MGD, although they have mostly studied patients who have MGD and dry eye . In this population-based study, the prevalence of MGD and its association with other ophthalmic and systemic diseases is investigated in an adult population of Shahroud, Iran 2. Methods In this study, data were used from the second phase of the Shahroud
Corresponding author at: Department of Epidemiology and Biostatics, School of Public Health, Tehran University of Medical Sciences, 14155-6446, Tehran, Iran. E-mail address: [email protected]
http://dx.doi.org/10.1016/j.clae.2017.05.003 Received 12 August 2016; Received in revised form 20 April 2017; Accepted 5 May 2017 1367-0484/ © 2017 Published by Elsevier Ltd on behalf of British Contact Lens Association.
Please cite this article as: Hashemi, H., Contact Lens and Anterior Eye (2017), http://dx.doi.org/10.1016/j.clae.2017.05.003
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Eye Cohort Study conducted in 2014. The Shahroud Eye Cohort Study is an epidemiological study on a random sample of 40–64 year old adult residents of Shahroud, which aims to identify the causes of eye disease and visual disorders. The details of the methodology and population sampling are described elsewhere . In brief, from the total population of 40 to 64 year old adults of about 28,000 people, 6311 individuals were selected through random cluster sampling, and 5190 participated in phase I of the study in 2009 (response rate: 82.2%). In the second phase of the study, all baseline participants (5190 people) were invited to have follow-up examinations and 4737 participated (response rate: 91.3%). After completing the interviews, all participants had comprehensive eye examinations including near and distance vision testing, refraction, slit lamp exam, and direct and indirect ophthalmoscopy. For each individual the necessary information in relation to anthropometric measures, blood pressure, lipid proﬁle, fasting blood sugar, and hemoglobin A1c level was recorded. The diagnosis of MGD was based on the clinical judgment of the study ophthalmologist. According to the international workshop on Meibomian gland dysfunction: Report of the diagnosis subcommittee , MGD can be clinically categorized into: 1. Asymptomatic MGD, 2. MGD with ocular surface damage, 3. MGD-related evaporative dry eye, and 4. MGD associated with other ocular disorders. In this study all subtypes of above deﬁnition were considered as MGD. MGD cases included both hypersecretory and hyposecretory types and the cases with Meibomian gland diseases excluded from MGD deﬁnition. This study was approved by the Ethics Committee of Shahroud University of Medical Sciences, and all study procedures adhered to the tenets of the Declaration of Helsinki for human research. Informed written consents were obtained from all participants.
Table 1 Prevalence of Meibomian gland dysfunction in at least one eye by gender, age, and other variables in the Shahroud, Iran, 2014.
2.1. Statistical analysis In this study, the prevalence of MGD and 95% conﬁdence intervals (CI) are provided for the total population as well as study subgroups. In order to investigate the relation between MGD with potential risk factors, simple and multiple logistic regression analyses were used. In the multiple logistic regression analysis model, the forward likelihood ratio method was used to remove non-signiﬁcant variables. Thus, the ﬁnal model with the remaining variables provided the adjusted odds ratio and 95% CI. In all analyses, the design eﬀect was calculated to correct for the eﬀect of cluster sampling on calculating the conﬁdence intervals. In all statistical tests, a signiﬁcance level of 0.05 was considered.
Number of participants
Prevalence% (95% Conﬁdence Intervals)
27.8 (25.4–30.2) 25.2 (23.2–27.2)
45–49 50–54 55–59 60–64 65–69
870 1262 1179 857 531
25.4 24.6 25.2 39.9 27.6
(22.2–28.5) (21.8–27.5) (22.6–28.0) (26.4–33.5) (24.0–31.3)
illiterate primary secondary high school college
525 1483 712 1454 522
29.5 26.9 27.1 24.7 24.2
(25.2–33.4) (24.0–29.8) (23.6–30.6) (21.9–27.5) (20.4–28.0)
< 25 ≥25
28.6 (25.3–31.8) 25.6 (23.8–27.5)
26.0 (24.2–27.8) 28.0 (24.4–31.5)
26.8 (24.9–28.6) 24.5 (21.5–27.4)
23.1 (20.8–25.5) 28.2 (26.1–30.3)
24.6 (22.5–26.7) 28.2 (25.9–30.5)
24.7 (22.9–26.5) 30.7 (27.7–33.7)
26.3 (24.5–28.1) 24.9 (20.1–29.6)
and subgroups. All variables of gender, age, years of education, BMI, and diabetes, as well as hypertension, Losartan use, HDL, and pinguecula were entered in simple logistic regression models. The ﬁrst 5 variables showed a p < 0.20 and were ﬁt in the multiple logistic regression model. The odds ratios obtained from univariate and multivariable logistic regression models are presented in Table 2. Variables which maintained their signiﬁcance in the ﬁnal model, in the order added to the model, were pinguecula (OR = 1.30, 95% CI: 1.12–1.50), hypertension (OR = 1.34, 95% CI: 1.11–1.61), HDL level (OR = 0.992, 95% CI: 0.986–0.999), diabetes mellitus (OR = 0.83, 95% CI: 0.71–0.97), and years of education (OR = 0.98, 95% CI: 0.96–0.99).
3. Results Of the 4737 participants, 37 cases had missing data and the ﬁnal analyses were therefore performed with data from 4700 people with a mean age ( ± SD) of 55.9 ± 6.2, and 2769 (58.9%) of them were women. In total, 1235 participants (26.3%, 95% CI: 24.5–28.1) were diagnosed with MGD in at least one eye, and in more than 99% of these cases, MGD was bilateral. Therefore, the prevalence rates of unilateral and bilateral MGD were 26.3% (95% CI: 24.5–28.1) and 26.1% (95% CI: 24.3–27.9), respectively. Considering MGD in at least one eye as the outcome measure, MGD prevalence was higher in men (27.8%, 95% CI: 25.4–30.2) than woman (25.2%, 95% CI: 23.2–27.2). Among the studied age groups, the 60–64 year age group (39.9%, 95% CI: 26.4–5.4) and among education categories, illiterate people (29.5%, 95% CI: 25.2–33.4) had the highest MGD prevalence rates. The prevalence of MGD was lower in people with body mass index (BMI) > 25 (25.6%, 95% CI: 23.8–27.5) compare to those with BMI < 25 (28.6%, 95% CI: 25.3–31.8). MGD was more common among smokers than non-smokers (28.0% vs. 26.0%). Table 1 shows the prevalence of MGD in at least one eye in the total study population
4. Discussion The MGD prevalence rates reported in the available literature broadly vary, but they generally point to higher rates in Asian populations compared to predominantly Caucasian populations . In the present study, the prevalence of MGD in the 45–69 year old population was 26.3% (95% CI: 24.5–28.1) which is lower compared to other studies conducted on Asian populations (from 46.2% in the Bangkok Study to 69.3% in the Beijing Eye Study) [13,17–19], but higher than population-based studies on Caucasians (from 3.5% in the Salisbury Eye Evaluation Study  to 19.9% in the Melbourne Visual Impairment Project ). Genetic predisposition of Asians or racial diﬀerences may be the cause of the higher prevalence of this disorder in the Asian race. However, due to diﬀerences in the study populations and deﬁnitions, it is diﬃcult to estimate the exact MGD prevalence rate in the general population, and drawing any comparison between studies or an overall conclusion must be done with caution. 2
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asymptomatic cases. In this regard, the population-based study by Siak et al.  did not ﬁnd a signiﬁcant relation between the male gender and MGD either. In the case-control study by Pinna et al. , gender showed no signiﬁcant eﬀect. Although the exact pathogenesis of the disease is not clear, multiple factors are known to lead to MGD [30,31]. Among possible etiologies, there is evidence conﬁrming the role of sex steroid hormones in causing MGD [1,30,32–36]. Laboratory studies have shown that androgens and estrogens can regulate the metabolism of Meibomian glands and control the gene expression and lipid production in these glands [37,38]. Hormonal change scan lead to diﬀerent types of MGD, and this usually happens after a course of estrogen replacement therapy or anti-androgen therapy [32,38]. In regards to the role of gender and the direction of it correlation with MGD, inter-study diﬀerences may be due to the type of MGD assessed in these studies. The precise mechanism through which sex hormones can cause MGD is still unclear. Despite the general agreement regarding the correlation between MGD and age [4,22,36,39–41], previous studies attribute the impact of aging to age-related atrophy of Meibomian gland acini and decreased lipid expression [2,42–44]. Other observed changes include focal hyper keratinization of the ductal epithelium, cystic dilation, and lipogranulomatoses, though their exact relation with age is not clear . In present study, limiting the sample to the middle-aged (45–69 years old) can be the reason for contradictory results. Based on the ﬁndings, a higher level of education was associated with reduced odds of MGD. In the study by Nemet et al. , the prevalence of diﬀerent types of blepharitis including posterior blepharitis, which occurs following Meibomian gland inﬂammation and dysfunction, was higher in populations with lower socioeconomic status and in urban areas with high population density. In this study, the relation of other socioeconomic factors with diﬀerent types of blepharitis did not investigated. The role of microbial factors and eyelid health in certain cases of MGD is well known . Hence, with regards to the role of these factors, a lower level of health in individuals with lower social economic status may explain the observed relationship. Unlike pterygium, the association between pinguecula and MGD maintained statistical signiﬁcance which is in line with the ﬁndings of other studies [1,27,47]. Pinguecula can disrupt tear ﬁlm coverage over the ocular surface, and therefore, may lead to the deterioration of MGD symptoms such as dry eye. A common factor may be causing both diseases. In the present study, no signiﬁcant correlation between MGD and smoking was found which was in line with Siak et al. , but in the study by Viso et al. , a signiﬁcant inverse relation was reported. A more detailed assessment of this variable in terms of the average number of cigarettes per day, number of years of smoking, etc. can help with a better assessment of the impact of smoking on MGD. It was also found a signiﬁcant inverse relation between HDL levels and MGD. Bukhari et al.  demonstrated that dyslipidemia correlated with the degree of MGD rather than its presence. In present study, the degree of MGD was not recorded. The relationship between hypercholesterolemia and MGD has been reported by others [7,8]. Dao et al.  studied the association of serum lipid proﬁle with MGD and observed that patients with moderate to severe MGD have a higher total cholesterol level compared to the general population, and the higher level of HDL was the main cause of the higher level of total cholesterol. In other words, unlike the ﬁndings in the present study, a higher serum HDL level was a risk factor for MGD with an unknown mechanism. In line with other studies [1,8], in present study a signiﬁcant relation between BMI and MGD was not found.
Table 2 The eﬀect of diﬀerent independent variables on Meibomian gland dysfunction (in at least one eye) in simple and multiple logistic regression models, Shahroud, Iran, 2014. P value
Crude Odds Ratio (95% Conﬁdence Interval)
Adjusted Odds Ratio (95% Conﬁdence Interval)
Sex (Male/ Female)
Reference 0.96 (0.79–1.16) 0.99 (0.81–1.2) 1.26 (1.01–1.56) 1.12 (0.89–1.40) 0.86 (0.73–1.01)
– 0.680 0.983 0.038 0.309 0.075
Reference – – – – –
– – – – – –
0.98 (0.97–0.99) 1.10 (0.93–1.30) 1.31 (1.14–1.51) 1.20 (1.05–1.38) 0.88 (0.76–1.03) 1.001 (1.000–1.002) 1.0001 (1.000–1.008) 0.99 (0.986–0.998) 1.35 (1.18–1.55) 0.93 (0.72–1.19)
0.019 0.26 < 0.001 0.007 0.122 0.348
0.98 (0.96–0.99) – 1.34 (1.11–1.61)
0.023 – 0.002
0.83 (0.71–0.97) –
0.992 (0.986–0.999) 1.30 (1.12–1.50) –
Age (Year) 45–49 50–54 55–59 60–64 65–69 Body Mass Index (≥25/ < 25) Education (year) Current Smoker Hypertension Losartan Use Diabetes Total Cholesterol Triglyceride HDL Pinguecula Pterygium
< 0.001 0.549
< 0.001 –
A number of clinic-based studies with smaller sample sizes have been conducted as well [21–25]. Since there are only few populationbased studies on this subject, the information in these clinic-based studies (though limited) can be used in regard to MGD prevalence and its related factors, although the accuracy and generalizability of their results may be limited. Since these studies are conducted on highly selective and speciﬁc groups of patients, comparing their ﬁndings with those from population-based studies can be diﬃcult. In this study, it was found a signiﬁcant positive correlation between MGD and hypertension, which is in line with other reports addressing this relationship. [1,26] This relation maybe an indirect inﬂammatory or hormonal eﬀect, but a direct eﬀect is possible as well. In present study, in contrast to the study by Siaket al. , the impact of Losartan did not maintain a statistical signiﬁcance in the multivariable model; however, in Siak et al. , study the impact of Losartanon on MGD was investigated in a multivariable model including diastolic blood pressure only without taking account of systolic blood pressure. In contrast to the study by Pathan , it was found a signiﬁcant inverse relationship between MGD and diabetes mellitus. The eyes, in general, and particularly Meibomian glands, are rich in arteries, and diseases aﬀecting blood vessels can impair blood delivery to these glands and lead to MGD . The direct impact of diabetes on MGD in the study by Viso et al.  was observed only in symptomatic cases, and Siak et al.  stated that the association was not statistically signiﬁcant. Lack of symptoms in certain diabetic cases has been attributed to probable sensory neuropathy. In the present study, the observed protective eﬀect of diabetes may be due to the lack of MGD symptoms in diabetic patients. On the other hand, the possible eﬀect of diabetes medications on lipid concentrations (serum lipids and lipid proﬁle) may explain the absence of this expected relation in present study [28,29]. Further studies are warranted to examine this association. In the present study, signiﬁcant association between MGD and gender was not found. In the population-based study by Viso et al. , a signiﬁcant relation with the male gender was only observed for
5. Conclusion The prevalence of MGD in present study is lower than the rates reported in studies of other Asian populations but higher compared to the reported rates in predominantly Caucasian populations. The 3
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