Purpose
To determine whether meibomian gland disease, a major contributor to dry eye syndrome, is associated with dyslipidemia.
Design
Retrospective case-control study.
Methods
setting: Clinical practice. patient or study population: Sixty-six patients from January 2008 to July 2009 with moderate to severe meibomian gland disease whose serum lipid levels were obtained. We excluded patients who were already taking lipid-altering substances and patients with rheumatologic disease. We analyzed several parameters in prevalence of dyslipidemia (total cholesterol > 200 mg/dL, low-density lipoprotein [LDL] > 130 mg/dL, high-density lipoprotein [HDL] < 40 mg/dL, and triglycerides >150 mg/dL) in MGD patients and compared these patients to the general population as reported by data from the National Health and Nutrition Examination Survey (NHANES). main outcome measure: The prevalence of dyslipidemia (elevated total cholesterol, elevated LDL, decreased HDL, or elevated triglycerides) in patients with moderate to severe MGD.
Results
Patients with moderate to severe MGD had a higher incidence of dyslipidemia with respect to elevated total cholesterol (>200 mg/dL), 67.4% to 45.1% ( P = .0012) when compared to population controls. There was a smaller number of MGD patients with low HDL (HDL < 40 mg/dL), 6.5%, when compared to controls, 15.7% ( P = .045). The incidence of increased LDL was not statistically significant ( P = .184). There was a statistically smaller number of MGD patients with high triglycerides (TG > 150 mg/dL), 15.2%, when compared to controls, 33.1% ( P = .0049).
Conclusions
Patients with moderate to severe MGD have a higher incidence of dyslipidemia with respect to elevated total cholesterol than the general population. Surprisingly, the component of total cholesterol that contributed most to this increase in total cholesterol came from elevated serum HDL levels. To our knowledge, elevated HDL has not been associated with any pathologic state. Patients with MGD had a statistically significant lower incidence of hypoalphalipoproteinemia (low HDL) than the general population. Patients with MGD also had a lower incidence of hypertriglyceridemia than the general population.
Ophthalmologists recognize that blepharitis, inflammation of the eyelid, is a common cause of dry eye syndrome. There are 2 types of blepharitis, anterior blepharitis and posterior blepharitis. Physical symptoms of both types of blepharitis include redness, foreign body sensation, itching, dry eye, crusting upon awakening, and blurred vision. Irritation of the outer eyelid is termed anterior blepharitis and is usually bacterial or parasitic in origin, while irritation of the inner eyelid is expressed as posterior blepharitis, caused primarily by the dysfunction of the meibomian glands.
The meibomian glands are holocrine, tubulo-acinar structures that secrete meibum, a substance composed of lipids that forms the most anterior layer of the tear film, inhibits the evaporation of the underlying aqueous layer, and prevents the development of dry eye. A single row of meibomian glands are located along the lid margin of both the superior and inferior eyelids.
The mucin and aqueous layers make up the remainder of the tear film. The mucin layer is secreted by goblet cells on the conjunctiva, which rests on the epithelial surface of the cornea and helps spread the aqueous layer evenly over the ocular surface. The aqueous layer is secreted by the lacrimal gland, represents 90% of the thickness of the tear film, and consists of a dilute solution of salts, minerals, and dissolved organic materials. An unstable tear film offers little protection, hydration, or lubrication to the ocular surface and is 1 of the major contributors to ocular surface disease.
Meibomian gland dysfunction (MGD) results from an altered composition of meibum or from outflow obstruction of the gland. Altered composition of the lipid layer may result in uneven coverage of the aqueous layer. Obstruction prevents meibum secretion, decreasing the amount of lipid content of the tear film and subsequent protection against early evaporation and early tear break-up. Thus, the unprotected epithelium can become irritated and damaged, leading to ocular surface disease. Dysfunctional tear syndrome is an extremely common condition and has recently been defined to include lid margin disease. Studies indicate that up to 20% of adults aged 45 years or more experience dry eye symptoms. Current treatment modalities include warm compresses, antibiotic ophthalmic drops, anti-inflammatory ophthalmic drops, and artificial tears. Recently, omega-3 fatty acid supplementation has been shown to be beneficial in the treatment of MGD. Despite these treatments, many patients do not experience complete resolution of their symptoms.
Lipid research has been focused primarily on cardiovascular and cerebrovascular disease risk. Total cholesterol was found to be composed of 3 main types of lipoproteins—low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL). Patients with cholesterol and lipoprotein serum values outside the normal range are defined as having dyslipidemia. It is well understood from epidemiologic studies that having elevated levels of LDL or decreased levels of HDL, with or without other risk factors, increases the risk of a cardiovascular event.
The prevalence of dyslipidemia in the general population is well described by current literature, which extrapolated data from the National Health and Nutrition Examination Survey (NHANES). The prevalence of total cholesterol greater than 200 is 45.1% and total cholesterol greater than 240 is 15.7%. The prevalence of LDL greater than 130 is 32.8%, HDL less than 40 is 15.5%, and triglycerides greater than 150 is 33.1%.
The purpose of this study is to determine the association of MGD with serum lipid profiles.
Materials and Methods
We reviewed the charts of patients in our clinic who were diagnosed with MGD since January 1, 2008. Treatment of our patients with MGD often includes the supplementation of 2000 to 4000 mg of an omega-3 fatty acid daily. Omega-3 fatty acid supplementation is known to alter lipid levels; therefore, we routinely order a baseline lipid panel, which includes HDL concentration, LDL concentration, triglycerides, and total cholesterol.
Patients were diagnosed with MGD by clinical examination based on glandular obstruction and meibum quality. This grading was obtained by gently applying pressure with a cotton swab tip to the upper and lower eyelid while observing the ease of excretion and quality of the meibum under slit-lamp microscopy.
Currently, there are no well-accepted clinical guidelines on describing meibomian gland obstruction or quality. We use a modified approach of Foulkes and Bron to grade meibomian gland obstruction on a scale from 0 (no obstruction) to 4 (complete obstruction). Meibum quality was graded on a scale from 0 (clear) to 4 (toothpaste-like). Patients graded 3 or higher on either of these scales in either eye during their baseline meibomian gland evaluation were diagnosed with moderate to severe meibomian gland dysfunction. We ordered lipid profiles on patients diagnosed with moderate to severe meibomian gland dysfunction at the time of diagnosis.
In patients diagnosed with moderate to severe MGD, we included those 20 years of age or older and excluded those previously taking statins or omega-3 fatty acid supplements, which are known to alter lipid levels. We also excluded patients with known rheumatologic disease, as this may confound the causation of MGD.
Age, sex, cholesterol-lowering medications, total cholesterol, HDL, LDL, and triglycerides were recorded. The percentage of patients with total cholesterol greater than 200 mg/dL, HDL less than 40 mg/dL, LDL greater than 130 mg/dL, and triglyceride levels greater than 150 mg/dL were determined and compared to historical controls.
Statistical Methods
The percentage of MGD patients whose total cholesterol level greater than or equal to 200 mg/dL was determined and a 1-sample z test was calculated to determine whether this percentage was significantly different than in the general population. Additionally, we stratified our patients by age and sex to compare to controls. Similarly, the percentages and z tests were used for the secondary outcome variables (LDL, HDL, and triglycerides).
We define statistically significant as a P value of less than .05.
Results
Baseline lipid levels were recorded for 63 patients with MGD. Of these, 2 patients were excluded because of rheumatologic disease and 15 patients were excluded from the analysis because of their taking either an omega-3 fatty acid supplement (n = 6) or a statin (n = 9). Of the 46 remaining patients, 22 were male and 24 were female, the average age was 52.0 years, and the range in age was 27 to 82. We stratified our patients into age brackets (age 20–44, n = 17 [male n = 8, female n = 9]; age 45–64, n = 18 [male n = 7, female n = 11]; age 65+, n = 11 [male n = 7, female n = 4]) to compare to historical controls gathered from the NHANES, which was population age-adjusted (average age = 46.6).
We found a statistically significant increase in the proportion of patients with elevated total cholesterol (total cholesterol > 200 mg/dL) ( Figure 1 ), 67.39% (31/46) when compared to controls, 45.1% ( P = .0012). There was a statistically smaller number of MGD patients with low HDL (HDL < 40 mg/dL), 6.5% (3/46), when compared to controls, 15.7% ( P = .045). There was an elevation prevalence of elevated serum LDL (LDL > 130 mg/dL) between patients with MGD and those in the general population (39.1% [18/46] and 32.8%), but this was not statistically significant ( P = .184). There was a statistically smaller number of MGD patients with high triglycerides (TG > 150 mg/dL), 15.2% (7/46), when compared to controls, 33.1% ( P = .0049).
