|Year : 2019 | Volume
| Issue : 3 | Page : 208-212
Study of meibomian gland dysfunction and hypercholesterolemia
Ashwin Segi, Kirti Nath Jha, Krishnagopal Srikanth
Department of Ophthalmology, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth, Puducherry, India
|Date of Submission||10-Feb-2019|
|Date of Decision||04-Mar-2019|
|Date of Acceptance||07-Mar-2019|
|Date of Web Publication||11-Nov-2019|
Dr. Kirti Nath Jha
Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth, Pondy-Cuddalore Main Road, Puducherry - 607 402
Source of Support: None, Conflict of Interest: None
Background: Hypercholesterolemia is a risk factor for ischemic heart disease and cerebrovascular disease. Increased cholesterol in the meibomian gland secretion has been considered necessary for development of meibomian gland dysfunction (MGD). Aim: To study the association of MGD with hypercholesterolemia in adults aged 20-60 years age. Setting and Design: Observational case-control study. Methods and Materials: We studied one hundred and twenty individuals aged 20-60 years divided into two groups; sixty cases of MGD and no known hypercholesterolemia; sixty controls with neither MGD nor hypercholesterolemia. Examination included anterior segment examination, tear film break-up time (TBUT), Schirmer's test and assessment of meibomian gland function. MGD was graded based on quality of meibum secretion and meibomian gland function (expressibility). Other investigations included lipid profile, random blood sugar, serum creatinine and body mass index (BMI). Statistical Analysis: We calculated proportion, mean, standard deviation, 95% confidence interval (CI), Z- test, and paired t-test for comparison between groups. Results: Hypercholesterolemia (i.e. serum cholesterol ≥ 200 mg/dl) was found in 39 (65%) and 31 (51.67%) among cases and control respectively. Hypercholesterolemia was found in 17 (44.7%) cases with grade 2 meibomian gland function (i.e. expressibility) (p=0.038) and 26 (68.4%) cases with grade 2 meibomian gland secretion (p = 0.037), these associations were statistically significant. Conclusions: Moderate MGD (i.e. grade 2 expressibility and secretion) is associated with elevated level of total cholesterol (i.e. serum cholesterol level ≥ 200 mg/dl).
Keywords: Dry eye, hypercholesterolemia, meibomian gland dysfunction
|How to cite this article:|
Segi A, Jha KN, Srikanth K. Study of meibomian gland dysfunction and hypercholesterolemia. TNOA J Ophthalmic Sci Res 2019;57:208-12
| Introduction|| |
Meibomian gland More Details dysfunction (MGD) is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. It may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease. Hypercholesterolemia (total cholesterol >200 mg/dl) is an important risk factor for cerebrovascular disease, ischemic heart disease, and peripheral vascular disease.
Recent studies indicate that patients with moderate-to-severe MGD have a high incidence of total blood cholesterol than the general population. Furthermore, the young- and middle-aged patients with MGD with no history of hypercholesterolemia may have higher blood cholesterol levels than the general population.,
This study aimed to investigate the association between MGD and hypercholesterolemia in young- and middle-aged adults aged 20–60 years. MGD may prove a marker for unknown hypercholesterolemia in case such an association between hypercholesterolemia and MGD exists.
| Material and Methods|| |
This observational case–control study was conducted at a rural tertiary care hospital from January 2015 to June 2016 with prior approval from the institutional human ethics committee. Individuals aged 20–60 years with MGD and no known hypercholesterolemia formed the cases; individuals without MGD and no hypercholesterolemia formed the controls.
Individuals aged below 20 and above 60 years were excluded. Individuals with infectious keratoconjunctivitis or inflammatory ocular surface diseases unrelated to MGD, history of recent ocular surgery, presence of corneal arcus and alterations of the lacrimal drainage system, concomitant topical ophthalmic medications, and those with history of topical ophthalmic steroids administration during 4 weeks preceding the study, treatment with systemic drugs affecting tearing, pregnancy, history of hypercholesterolemia or intake of lipid-lowering drugs, diabetes mellitus or any other systemic, neurologic, rheumatologic, or dermatologic disorder affecting the health of the ocular surface were also excluded from the study.
Examination included height in meters and body weight in kilograms and calculation of body mass index (BMI = weight in kg/height in m2). Biochemical parameters included lipid profile, random blood sugar, and serum creatinine. Eye examination included anterior segment examination and dilated fundus examination. MGD was diagnosed on the basis of meibomian gland expression and the quality of meibum; the meibomian gland secretion and function was noted by expressing the glands under the slit lamp with the index finger.
The meibomian gland expression was done by applying digital pressure through the substance of the lid. The procedure involved digital expression of secretion from the central glands with a force that does not require the application of a rigid surface on the conjunctival aspect of the eyelid. As such, when the eyelids are normal, light expression sufficed. Heavy pressure was avoided as it may express presecretory lipids from the acini. The process involved assessment of all three portions (lateral, middle, and the medial) of the lower eyelid margin.
Meibomian gland function was graded as follows: 0 (no obstruction - meibum easily expressed), 1 (mild obstruction - meibum expressible with mild pressure), 2 (moderate obstruction - meibum expressible with moderate pressure), and 3 (complete obstruction - no glands expressible, even with hard pressure).,, The quality of expressed meibum was graded as follows: 0 (clear fluid), 1 (cloudy fluid), 2 (cloudy particulate fluid), and 3 (toothpaste-like)., Tear film break-up time (TBUT) and Schirmer's test were also recorded. TBUT is the interval in seconds between a complete blink and the appearance of the first randomly distributed dry spot on the fluorescein sodium-stained precorneal tear film seen under the cobalt blue filter of the slit lamp.
Schirmer's test is employed for quantitative assessment of aqueous tear. It was performed by placing Whatman filter paper 41 (5 mm × 35 mm) in the lower conjunctival fornix, at the junction of outer one-third and inner two-third for 5 min. The measurement of wetting (in mm) after 5 min was taken as a measure of aqueous tear secretion. We did not use topical anesthetic during the procedure. Each eye was tested separately.
The analysis of the data was carried out using Microsoft Office Excel 2007 and IBM SPSS Statistics version 20 (IBM Corp, Armonk, NY, USA). We calculated proportion, mean, standard deviation, 95% confidence interval (CI), Z-test, and paired t-test for comparison between groups. P ≤ 0.05 was considered as statistically significant.
| Results|| |
The study population included 120 individuals; 60 cases of MGD and 60 controls without MGD. There were 51 males and 69 females; M: F ratio 0.74. Among the cases, there were 23 (38.3%) males and 37 (61.67%) females. Controls included 28 (46.67%) males and 32 (53.3%) females [Table 1]. The average age of the cases was 54.8 ± 5.6 years. The average age of the controls was 52.3 ± 6.4 years. The difference of age among cases and controls was not statistically significant.
Average BMI of the cases was 23.5 ± 1.9 kg/m2 and the controls was 23.4 ± 1.8 kg/m2, respectively, (P = 0.78). Average serum cholesterol among the cases was 204.7 ± 20.7 mg/dl, among the controls was 198.03 ± 23.7 mg/dl, (P = 0.11). Average triglyceride level among the cases was 141.4 ± 36.2 mg/dl and among the controls was 145.5 ± 29.1 mg/dl, (P = 0.49). Mean biochemical parameters of the cases and the controls are shown in [Table 2].
The age-wise stratification of cases and controls into three groups and comparison of serum cholesterol between these subgroups did not reveal any statistical difference in cholesterol level among the cases and controls in the age groups ≤40 and 41–50 years. In the age group, 51–60 years, the cases and the controls had serum cholesterol values of 209.09 ± 20.15 mg/dl and 197.84 ± 14.79 mg/dl, respectively. This difference was found to be statistically significant (P = 0.006) [Table 3].
|Table 3: Comparison of total cholesterol levels among cases and controls|
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On the basis of expressibility, 6 (10%) cases had Grade 0 meibomian gland function, 31 (51.67%) cases Grade 1 meibomian gland function, 21 (35%) cases had Grade 2 meibomian gland function, and 2 (3.33%) cases had Grade 3 meibomian gland function [Table 4].
On the basis of quality of secretion, 2 (3.33%) cases showed Grade 0 meibomian gland secretions, 19 (31.67%) cases showed Grade 1 secretion, 33 (56.6%) cases showed Grade 2 meibomian gland secretions, and Grade 3 secretion was seen in 4 (6.67%) cases [Table 5]. In two patients, those with obstructive MGD, secretion quality could not be graded. We noticed that only 4 (18.18%) individuals with serum cholesterol <200 mg/dl needed moderate pressure to express meibomian secretion (i.e., Grade 2). Among those with serum cholesterol, ≥200 mg/dl 17 (44.73%) fell into Grade 2 meibomian gland function (Z score = 2.0782, P = 0.038) [Table 6]. This association was found statistically significant.
|Table 6: Meibomian gland function (expressibility) and cholesterol levels|
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We noticed only 8 (40%) individuals with serum cholesterol <200 mg/dl had cloudy white secretion with particulate material (i.e. Grade 2), among those with serum cholesterol ≥200 mg/dl 26 (68.4%) fell into Grade 2 meibomian gland secretion (Z score = 2.0889, P = 0.037) [Table 7].
This association was found statistically significant. (Odd ratio = 3.25, 95% CI = 0.39–26.92). The odds ratio was compared between Grade 2 and Grade 3 secretions. To find differences of their association with cases of MGD and controls, we carried out stepwise logistic regression analysis including age, sex, BMI, triglyceride, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-LDL (VLDL), and glucose as covariates. MGD showed negative association with increased blood HDL (P = 0.047, 95% CI, 0.874–0.999). Increase in age showed positive correlation with MGD (P = 0.035, 95% CI, 1.005–1.161). Sex, BMI, total cholesterol, LDL, VLDL, and blood glucose did not show statistically significant association with MGD.
| Discussion|| |
The prevalence of MGD, a common cause of chronic ocular irritation varies from 3.5% to 70% in various series. MGD occurs due to change in composition of meibum or an obstruction of the meibomian glands which occurs secondary to hyperkeratinization of the duct epithelium and plugging with a solidified secretion. The resulting changes in tear film lipid layer lead to increased evaporation and tear osmolarity, and signs and symptoms of dry eye. The composition of meibum is mainly of wax and neutral sterol esters (~60%), with lesser quantities of polar lipids, triglycerides, free fatty acids, and free sterols. Cholesterol esters are present in patients with MGD. Studies have also hypothesized that increased cholesterol in the glandular secretion might have a role in the pathogenesis of MGD., Increase in cholesterol concentration in meibum results in increase in its melting point, and viscosity. These changes in meibum result in meibomian gland plugging and development of MGD.
Hypercholesterolemia is a risk factor for ischemic heart disease, cerebrovascular disease, and peripheral vascular disease. There are three main types of lipoproteins in total cholesterol: LDL, HDL, and VLDL. Raised levels of LDL or decreased levels of HDL have been reported to increase the risk of cardiovascular disease. MGD Grade 2 and above were seen more frequently among individuals with hypercholesterolemia (i.e., ≥200 mg/dl) in this study. Since MGD Grade 2 and above alone are symptomatic, it may be stated that symptomatic MGD is associated with hypercholesterolemia. Results of this study thus find support from an earlier study that noted similar association., We also found the association between meibomian gland function (expressibility) and cholesterol levels; majority of the cases with Grade 2 expressibility had hypercholesterolemia (i.e., ≥200 mg/dl) (P = 0.038). Hypercholesterolemia (i.e., ≥200 mg/dl) was found associated with alterations in meibomian gland secretions also. Most cases (68%) with Grade 2 secretion had higher than normal cholesterol levels. These observations support our premise of association between hypercholesterolemia and MGD. Due to the limited sample size, it is not possible to comment on the association between hypercholesterolemia and severe MGD (Grade 3 meibomian gland secretion and meibomian gland expressibility). We did not take into consideration among cases Grade 0 and Grade 1 meibomian gland secretion and function since they are rarely associated with dry eye syndrome.
Other workers also have noted a higher incidence of hypercholesterolemia in patients with moderate-to-severe MGD in comparison to the general population. Increase in cholesterol level occurred from increased HDL level. However, in our study, MGD showed a negative association with increased blood HDL (P = 0.047, 95% CI, 0.874–0.999). Pinna et al. also noted that young- and middle-aged patients with symptomatic MGD and with no history of hypercholesterolemia may have higher blood cholesterol level than controls of similar age without MGD. However, study by Pinna et al., is limited by its small sample size restricted to people from Italian ancestry.
Cholesterol levels among different age groups within cases and controls in our study reveal higher mean cholesterol level among the individuals aged 51–60 years. Increasing age correlates also with increase in the total cholesterol levels and MGD. In view of a few subjects (total: three) between 20 and 40 years, we are not in a position to opine on the association between MGD and hypercholesterolemia in young adults.
Relatively small sample size remains the only limitation of this study. Therefore, this study may be considered a pilot study that needs validation on a larger population. Our findings, if validated on a larger population, open the possibility of MGD diagnosed during ophthalmic consultation being the first indication of undiagnosed hypercholesterolemia.
| Conclusion|| |
Among young and middleaged adults aged 20–60 years, individuals with moderate MGD have a higher incidence of hypercholesterolemia than the healthy controls.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Nelson JD, Shimazaki J, Benitez-del-Castillo JM, Craig JP, McCulley JP, Den S, et al.
The international workshop on meibomian gland dysfunction: Report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci 2011;52:1930-7.
Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB, et al.
Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-47.
Pinna A, Blasetti F, Zinellu A, Carru C, Solinas G. Meibomian gland dysfunction and hypercholesterolemia. Ophthalmology 2013;120:2385-9.
Dao AH, Spindle JD, Harp BA, Jacob A, Chuang AZ, Yee RW, et al
. Association of dyslipidemia in moderate to severe meibomian gland dysfunction. Am J Ophthalmol 2010;150:371-75.
Tomlinson A, Bron AJ, Korb DR, Amano S, Paugh JR, Pearce EI, et al.
The international workshop on meibomian gland dysfunction: Report of the diagnosis subcommittee. Invest Ophthalmol Vis Sci 2011;52:2006-49.
McCulley JP, Shine WE. Meibomian gland function and the tear lipid layer. Ocul Surf 2003;1:97-106.
Linton RG, Curnow DH, Riley WJ. The meibomian glands: An investigation into the secretion and some aspects of the physiology. Br J Ophthalmol 1961;45:718-23.
Brown SI, Dervichian DG. The oils of the meibomian glands. Physical and surface characteristics. Arch Ophthalmol 1969;82:537-40.
Nichols KK, Foulks GN, Bron AJ, Glasgow BJ, Dogru M, Tsubota K, et al.
The international workshop on meibomian gland dysfunction: Executive summary. Invest Ophthalmol Vis Sci 2011;52:1922-9.
Schaumberg DA, Nichols JJ, Papas EB, Tong L, Uchino M, Nichols KK, et al.
The international workshop on meibomian gland dysfunction: Report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci 2011;52:1994-2005.
Driver PJ, Lemp MA. Meibomian gland dysfunction. Surv Ophthalmol 1996;40:343-67.
Tiffany JM. The role of meibomian secretion in the tears. Trans Ophthalmol Soc U K 1985;104 (Pt 4):396-401.
Butovich IA. The meibomian puzzle: Combining pieces together. Prog Retin Eye Res 2009;28:483-98.
Shine WE, McCulley JP. The role of cholesterol in chronic blepharitis. Invest Ophthalmol Vis Sci 1991;32:2272-80.
Krenzer KL, Dana MR, Ullman MD, Cermak JM, Tolls DB, Evans JE, et al.
Effect of androgen deficiency on the human meibomian gland and ocular surface. J Clin Endocrinol Metab 2000;85:4874-82.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult treatment panel III). JAMA 2001;285:2486-97.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]