Abstract
Purpose:
Dry eye disease (DED) is because of a decrease in the tear film’s volume or a change in the composition of tears. Evaporative dry eye is the most common type, which is due to meibomian gland dysfunction (MGD). In this study, the morphology of meibomian glands was evaluated in all kinds of dry eyes to look for any loss of meibomian glands, assess the function of remaining glands, and investigate the relationship between anatomy, function, and severity of DED.
Methods:
A total of 300 patients were included in the study, with 150 eyes in the study group and 150 in the control group. Meibomian gland morphology was assessed by examining the tarsal plate after everting the eyelids. Tear film function was evaluated using tear film break-up time (TBUT) and Schirmer’s test (SCH I and II). Meibomian gland morphology was examined with a slit-lamp under magnification, a transilluminator using a small light emitting diode (LED) bulb, and non-contact meibography using an auto refracto-keratometer (ARK).
Results:
Females had a higher prevalence of dry eyes in our study. In all, 103 eyes (68.6%) in the study group had evaporative dry eye, making it the most prevalent type. Among the 150 controls, 104 controls with 69.3% had no dry eye symptoms, and in those with symptoms, the evaporative type was the most common, with a 28% prevalence.
Conclusion:
TBUT should be performed in all patients with detectable MG abnormality. Meibography has high specificity and sensitivity to diagnose MGD and in turn dry eyes and should be considered a routine screening modality.
Keywords: Dry eye, evaporative dry eye, meibography, meibomian gland dysfunction, meibomitis, Schirmer’s test, tear film break-up time
Dry eye is the most common ophthalmological diagnosis[1] and is defined as a disease of tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is also accompanied by increased osmolarity of the tear film and inflammation of the ocular surface, according to the international dry eye workshop 2007 (DEWS).[2]
A decrease in tear film volume or composition of tears results in dry eye disease (DED).[3] Etiologically, DED is classified into the evaporative and aqueous deficient dry eye, with the former being more common.[4] Meibomian gland dysfunction (MGD) is a chronic, diffuse abnormality of meibomian glands commonly characterized by terminal duct obstruction or qualitative or quantitative changes in glandular secretion by an international workshop on MGD. It is the most common cause of evaporative dry eye.[4]
Tear film osmolarity determination is gaining importance and is now considered the “gold standard” test for diagnosing DED.[5] In MGD, glands become obstructed, and lipids stagnate, becoming thick, saturated, and stagnant, altering the morphology and even leading to atrophy of the glands.[6] Visualizing the morphology of meibomian glands through the conjunctiva in the tarsal plate is called meibography,[7] initially reported by Tapie in 1977.[8]
This study is mainly conducted to evaluate the morphology of meibomian glands in all types of dry eyes to look for any loss of meibomian glands, assess the function of remaining glands, and investigate the relationship between anatomy, function, and severity of DED.
Methods
It was a cross-sectional comparative study conducted in a tertiary health care center for 2 years, from September 2016 to August 2018, after taking adequate approval from the Institutional Ethics Committee.
With a 95% confidence level and 80% power with 6% absolute precision (with respect to Rege et al.), the sample size came to be 139. Hence, we took 150 cases and 150 controls. All patients with dry eye disease were included in the study, and patients with dry eye complaints during the immediate postoperative period and those with keratitis and epithelial defect were excluded from this study. Patients who visited our outpatient department with no dry eye symptoms were taken as controls and were age-matched with the cases.
All patients were examined after taking a good history and clinical examination, including a distant vision test using Snellen’s chart and a near vision test using Jaeger’s chart. We used a slit lamp for anterior segment examination. Special attention was paid to assessing the morphology of meibomian glands by examining both the tarsal plates after everting the lids under magnification. Fundus examination was performed using both direct and indirect ophthalmoscopy. Functions of tear film were assessed using tear film break-up time (TBUT) and Schirmer’s test I and II (SCH I and SCH II). Based on TBUT, the dry eye is graded as shown in Table 1. The severity of aqueous deficient dry eye was graded depending on the SCH I results [Table 2]. SCH II is performed only in patients with an abnormal SCH I result. A slit lamp was used to examine meibomian gland morphology under magnification, followed by a transilluminator using a small LED bulb. Findings were documented using an auto refracto-keratometer (ARK).
Table 1.
Based on TBUT, the dry eye is graded as follows
| TBUT | Severity of the dry eye |
|---|---|
| >8-10 s | Mild |
| 6-8 s | Moderate |
| 5 s or less | Severe |
Table 2.
The severity of dry eye was graded depending on the SCH I result
| Schirmer’s test | Severity of the dry eye |
|---|---|
| 11-15 mm | Mild |
| 6-10 mm | Moderate |
| 5 mm or less | Severe |
Transillumination meibography is performed using a small red LED bulb. This bulb was applied to the cutaneous side after everting the eyelid, and it allows observation of gland morphology from the palpebral conjunctival surface. The appearance of glands, duct dilation, and percentage of gland loss or dropout in both lids were analyzed. Meiboscores for upper and lower eyelids were summed to obtain a score for each eye; a photograph was taken for the same. Arita et al. grading was followed to grade the area of MG loss.[4]
Merits of this procedure: Meibography in our study was performed using the ARK, which is readily available in almost all ophthalmological setups. The red LED bulb is also readily available at nearby electronic stores. Hence, this technique can be performed easily in all setups with equipment already available with no additional cost to visualize the meibomian gland morphology and analyze the MG [Figs. 1-4 and Table 3]. Documentation of non-contact meibography was performed using ARK.
Figure 1.
LED bulb used in trans illumination meibography. This is applied to the cutaneous side after everting the eyelid and it allowed the observation of gland morphology
Figure 4.
Transillumination meibography showing abnormally dilated glands in the lower eyelid
Table 3.
Arita et al.’s grading
| Grade | Area of gland loss |
|---|---|
| Grade 0 | No loss of meibomian glands |
| Grade 1 | Area loss of less than one-third of the total MG area |
| Grade 2 | Area loss between one-third and two-thirds of the total MG area |
| Grade 3 | Area loss of more than two-thirds of the total MG area |
Figure 2.
Appearance of normal-looking glands in the lower eyelid using transillumination meibography
Figure 3.
Transillumination meibography of the upper eyelid showing normal-looking glands
The data analysis was done using Student’s unpaired t-test and statistical package SPSS, and the Chi-square test was used for the analysis. P value < 0.05 was considered significant.
Results
This cross-sectional study included 150 dry eyes (study group) and 150 control eyes. We studied the anatomy and function of MG in each group and compared the area of gland loss with the severity of dry eye in each group [Table 4 and 5]. The prevalence in females was more than that in males.
Table 4.
Age distribution
| Age | Study group | Control group |
|---|---|---|
| 30 and below | 8 (5.3%) | 8 (5.3%) |
| 31-40 | 15 (10%) | 15 (10%) |
| 41-50 | 39 (26%) | 39 (26%) |
| 51-60 | 46 (30.7%) | 46 (30.7%) |
| 61-70 | 28 (18.7%) | 28 (18.7%) |
| 71-80 | 12 (8%) | 12 (8%) |
| Above 80 | 2 (1.3%) | 2 (1.3%) |
Table 5.
Gender distribution in the study and control groups
| Sex | Study group | Control group |
|---|---|---|
| Female | 87 (58%) | 86 (57.3%) |
| Male | 63 (42%) | 64 (42.7%) |
The patients were classified into aqueous deficiency dry eye, mixed dry eye, and evaporative dry eye based on the results of SCH I and II, TBUT, and trans illumination meibography. Patients with SCH I or II alone less than 10 mm with TBUT >10 s and normal MG morphology were diagnosed with aqueous deficiency dry eye. Patients with SCH I or II greater than 10 mm with TBUT <10 s with or without abnormal MG morphology were diagnosed with evaporative dry eye disease. Patients with SCH I or II less than 10 mm and TBUT <10 s with or without abnormal MG morphology were diagnosed with mixed type of dry eye [Table 6-8, Figs. 5-10].
Table 6.
Percentage of evaporative dry eye is 68.6%
| Type of dry eye | Number of eyes | % |
|---|---|---|
| Aqueous deficient | 13 | 8.7 |
| Evaporative | 103 | 68.6 |
| Mixed | 34 | 22.7 |
Table 8.
Correlation of various factors in the total population
| Spearman correlation | ||||||
|---|---|---|---|---|---|---|
|
| ||||||
| Group | Age | TBUT | SCH1 | Anatomical gland loss | ||
| Cases | Age | Pearson correlation | -0.568** | -0.035 | 0.423** | |
| P | 0.000 | 0.668 | 0.000 | |||
| n | 150 | 150 | 150 | |||
| TBUT | Pearson correlation | ** | 0.112 | -0.563** | ||
| P | 0.174 | 0.000 | ||||
| n | 150 | 150 | ||||
| SCH1 | Pearson correlation | 1 | -0.182 | |||
| P | 0.026 | |||||
| n | 150 | |||||
| Anatomical gland loss | Pearson correlation | ** | ** | |||
| Control | Age | Pearson correlation | -0.648** | -0.051 | 0.690** | |
| P | 0.000 | 0.533 | 0.000 | |||
| n | 150 | 150 | 150 | |||
| TBUT | Pearson correlation | ** | 0.041 | -0.709** | ||
| P | 0.622 | 0.000 | ||||
| n | 150 | 150 | ||||
| SCH1 | Pearson correlation | -0.012 | ||||
| P | 0.887 | |||||
| n | 150 | |||||
| Anatomical gland loss | Pearson correlation | ** | ** | |||
Figure 5.
Among 150 eyes with dry eyes, 103 eyes (68.6%) had evaporative dry eye, making it the most prevalent dry eye. Next most common type of dry eye was mixed type seen in 34 eyes (22.7%) followed by aqueous deficient dry eye seen in 13 eyes (8.7%), making it the least prevalent
Figure 10.
Fifty-six eyes out of 150 eyes of the control group had dry eyes. In all, 48 eyes (85.7%) out of 56 had gland loss. Among 94 normal eyes, 16 eyes (17.02%) had gland loss and all of them had grade 1 gland loss
Table 7.
Prevalence of dry eye in the control group
| Type of dry eye | Number of eyes | % |
|---|---|---|
| Aqueous | 0 | 0% |
| Evaporative | 42 | 28% |
| Mixed | 4 | 2.7% |
Figure 6.
104 eyes were normal (69.3%). 30.7% had dry eye (28% evaporative dry eye + 2.7% mixed dry eye). Most common cause of dry eye was due to evaporation in control group
Figure 7.
Among dry eyes due to evaporation,16.5%(17) had mild, 69.9%(72) had moderate and 13.6%(14) had severe dry eye. Among eyes with mixed dry eye 35.3%(12) had mild, 47.1%(16) had moderate and 17.6%(6) had severe dry eye. Among eyes with aqueous deficiency dry eye, all had mild form and none had moderate or severe dry eye
Figure 8.
Among 42 eyes with evaporative dry eye in control group majority 59.5% (25) had mild dry eye and 40.5%(17) had moderate dry eye. Among 4 eyes with mixed dry eye 75%(3) had mild and 25%(1) had moderate dry eye
Figure 9.
50 eyes with grade 0 gland loss in study group, out of which 48% (24) had mild ,44% (22) had moderate and 8% (4) had severe dry eye. Out of 26 eyes with grade 1 gland loss majority had moderate 73.1% (19) followed by mild 19.2% (5) and severe 7.7% (2) dry eye. Among 29 eyes with grade 3 gland loss 55.2% (16) had severe, 44.8% (13) had moderate dry eye and none had mild disease
In both groups, age was negatively correlated to TBUT and SCH I, that is, TBUT decreased as age increased, indicating an increase in the severity of dry eye as age increased. Age was positively correlated to the area of gland gloss in both groups. As the age increased, the area of gland loss increased. Also, TBUT and SCH I were negatively related to the area of gland loss, inferring that as the area of gland loss increased, the severity of dry eye increased.
Discussion
We compared 150 dry eyes with 150 control eyes in this cross-sectional study. We mainly emphasized objective tests such as trans illumination meibography, TBUT, and Schirmer’s test to evaluate the severity. Messmer et al., in their study, mentioned that clinical findings do not always correlate with clinical signs and vice versa.[9]
The prevalence of different types of dry eye and meibomian gland assessment was assessed in both groups, and their association was determined. Among the controls, a prevalence of 30.7% of dry eye was found, whereas Rege et al. had a prevalence of 15.4%.[10]
Our study group had 89.4% of patients above 40 years of age and 15.3% below 40 years of age. Moss et al. concluded that the incidence of dry eye increases with age, with a 13% rate of occurrence in patients aged 48–91 years.[11] Rege et al. also mentioned in an Indonesian study an increase in the prevalence of dry eye by 37.6% in the older population.[10]
A retrospective study conducted at The Miami and Broward Veterans Affairs eye clinics estimated a prevalence of 22% DED in females compared to 12% in males.[12] Females outnumbered males in both groups, and no similar statistically significant difference was noted (P = 0.01) in our study.
Evaporative dry eye is the most prevalent (68.6%) type in the study population. Among 150 control eyes, the prevalence of dry eye was 30.7%, with evaporative dry eye being the most common type (28%). However, no patient in the control group had any symptoms, which makes dry eye due to evaporation the most prevalent, similar to the study by Rege et al.[10]
Cuevas et al. mentioned MGD as the most common cause of mild to moderate evaporative dry eye and that all subjects of their study had symptomatic MGD.[5] Rege et al. concluded that lipid layer anomaly dry eye was the most prevalent type of dry eye in their study.[10] A study mentioned that the prevalence of dry eye was 95% in patients with blocked meibomian glands.[13] This occurrence of MGD in dry eye is statistically highly significant (P = 0.000) in our study.
We compared the anatomy and function of the meibomian glands using meibography by comparing the severity of dry eye with an area of gland loss. We had 50 eyes with grade 0 gland loss in the study group, of which 48% had mild, 44% had moderate, and 8% had severe dry eyes. Out of 26 eyes with grade I gland loss, the majority had moderate (73.1%), followed by mild (19.2%) and severe (7.7%) loss. Among 29 eyes with grade 3 gland loss, 55.2% had severe, 44.8% had moderate dry eye, and none had mild disease. The severity of dry eye increased with an increase in the area of gland loss in our study and was statistically significant (P = 0.000) in our study population.
Fifty-six eyes out of 150 eyes in the control group had dry eyes. Also, 48 eyes (85.7%) out of 56 eyes had an area of gland loss. Among 94 with no dry eye, 16 eyes (17.02%) had gland loss and all of them had grade 1 gland loss. In the control group, the area of gland loss was significantly associated with the severity of dry eye. The area of gland loss increased as age increased, which was highly significant (P = 0.000).
We correlated the findings obtained from both groups. In both the groups, age was negatively correlated to TBUT and SCH I, that is, TBUT decreased (which indicates an increase in the severity of dry eye) as age increased. Age was positively correlated to the area of gland gloss in both groups. As the age increased, the area of gland loss increased. Also, TBUT and SCH I were negatively related to the area of gland loss, inferring that as the area of gland loss increased the severity of dry eye also increased.
Conclusion
Evaporative dry eye was the most prevalent type with a prevalence of 68.6% in our study, with MGD being the common cause. The prevalence of dry eye was common after 40 years (89.4%) and significantly increased with age (P = 0.004). MGD not only associates but also determines the dry eye severity. The severity of dry eye is positively correlated with the area of gland loss with high statistical significance (P = 0.000). The area of gland loss was also seen in old age and the severity of gland loss increased significantly with age. TBUT and area of gland loss had a negative correlation. The severity of the symptoms may vary from the clinical findings.
Therefore, we suggest that TBUT should be performed in all patients with detectable MG gland abnormality to assess the function. Meibography has high specificity and sensitivity to diagnose MGD and dry eye and it can be performed in any setting with an auto-refractometer easily. Meibography should be considered a routine screening modality in dry eye patients.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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