Prevalence of Meibomian Gland Atrophy in Patients Undergoing Cataract Surgery : Cornea

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Prevalence of Meibomian Gland Atrophy in Patients Undergoing Cataract Surgery

Yeu, Elizabeth MD*; Koetting, Cecelia OD, FAAO; Calvelli, Hannah OD

Author Information
Cornea ():10.1097/ICO.0000000000003234, January 12, 2023. | DOI: 10.1097/ICO.0000000000003234
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Abstract

Meibomian gland dysfunction (MGD) is the most common cause of dry eye disease (DED). An estimated 86% of patients with DED have MGD as a primary or contributing component of their condition.1 MGD is a progressive disease that gets worse the longer it goes untreated. Over time, the glands may become obstructed, potentially leading to meibomian gland (MG) atrophy. The prevalence of MG atrophy in normal healthy adults is reported to be as high as 72% and is believed to significantly increase with age.2–6 Because cataract surgery is commonly performed in older patients, an increased likelihood of MG atrophy in this population can be anticipated.

MGD-associated DED alters the tear film and overall integrity of the ocular surface, which is vital for refractive planning of cataract surgery. An unstable tear film in patients with cataract may lead to erroneous keratometric measurements during the preoperative workup, thus leading to inaccurate intraocular lens (IOL) calculations and presurgical planning for astigmatism management.7 Cataract surgery itself has been reported to induce DED and/or exacerbate preexisting DED.8 An unstable tear film may impair visual quality and aggravate postoperative ocular irritation, potentially leading to poor patient satisfaction, even among patients who have achieved good uncorrected visual acuity.

The MGD Workshop Report documented a strong association between MG dropout and MGD severity and recommends performing baseline meibography when possible.9 Recent advances in imaging devices have allowed clinicians to perform high-quality in-office meibography to assess MG architecture and atrophy.2,10,11 Given these recommendations and the potential impact of MGD on surgical planning and IOL selection, meibography is routinely performed in all patients scheduled to undergo cataract surgery at the author's clinical practice. This study was aimed at determining the prevalence of MG atrophy in a US-based population of patients presenting for cataract surgery evaluation.

METHODS

This retrospective study included case records of patients presenting for cataract surgery at Virginia Eye Consultants, Norfolk, VA, between June and December 2020. The study was conducted in compliance with the study protocol and followed the tenets of the Declaration of Helsinki and its amendments. Salus Independent Review Board (Austin, USA) approved the study with a waiver of informed consent as the data were recorded in patient charts as a part of routine clinical practice, and only deidentified patient data were analyzed.

Patients aged 50 years or older who had undergone a preoperative cataract surgery workup with meibography (LipiScan, Johnson & Johnson Vision, Santa Ana, CA) to evaluate MG structure were included in the study. Case records of patients for whom clear meibography images could not be obtained were excluded.

Grading of MG structure was performed as described previously by Arita et al.12 The amount of atrophy in the lower eyelid was semiquantitatively assessed and graded (grade 0 = no atrophy, grade 1 = 1%–33% atrophy, grade 2 = 34%–66% atrophy, and grade 3 = more than 66% atrophy). MG function was assessed with 2 metrics: meibum expressibility was rated as easy, moderate, or difficult. Expressibility was performed by a single surgeon, digitally compressing the central lower lid margin for 5 seconds. Meibum secreted from each gland was graded on a scale of 1–4 (grade 1 = olive oil (clear liquid), 2 = cloudy, 3 = cloudy with debris, and 4 = toothpaste-like). Finally, telangiectasia was scored on a scale of 0–4, with 0 = no findings, 1 = mild telangiectasia, 2 = moderate telangiectasia, 3 = severe telangiectasia, and 4 = florid telangiectasia.

The chief outcome measure was the proportion of patients with MG atrophy of grade 0, 1, 2, and 3 on meibography. The association of MG atrophy with age, sex, ethnicity, various comorbidities (glaucoma, hypertension, diabetes mellitus, and autoimmune disease), previous DED diagnosis, the use of cyclosporine/lifitegrast for dry eye treatment, meibum grade, telangiectasia score, and history of smoking was also evaluated.

Data corresponding to only 1 eye per patient were included for analysis to avoid bias resulting from intereye correlation. If only 1 eye of a patient underwent cataract surgery during the study period (other eye not operated/operated outside the study period), that eye was the study eye. In cases where both eyes were available, only the right eye was included in the analysis.

Statistical Analysis

Statistical analysis was performed using SPSS software version 27.0 (IBM Corp, NY). Continuous data were described using descriptive statistics (mean and standard deviation), and categorical data were described using the participant count and percentage in each category. The association between MG atrophy and patient characteristics or risk factors was assessed using logistic regression. The McNemar test was used for paired nominal data. A P value of <0.05 was considered statistically significant.

RESULTS

Three hundred ninety-one eyes (391 patients) met the inclusion criteria and were included in the study. The mean age of patients was 68.5 ± 7.8 years (range: 50–90 years). The study population was 60.1% (n = 235/391) female and 39.9% (n = 156/391) male.

Figure 1 shows the prevalence of MG atrophy by grade. There were no statistically significant differences in overall MG atrophy when stratified by age of cohort, sex, or race (Table 1). Although MG atrophy was found to have a weak positive correlation with MG expressibility, meibum grade, and telangiectasia, only the correlation with expressibility was statistically significant (Table 2). The correlation between MG atrophy and the combined score of meibum expressibility and meibum grade was also statistically significant.

F1
FIGURE 1.:
Prevalence of MG atrophy by severity grade.
TABLE 1. - Demographic Characteristics
Characteristics N Meibomian Gland Atrophy P
Grade 1 Grade 2 Grade 3 Grade ≥1
Age
 ≥50 and <60 56 44.6% 21.4% 28.6% 94.6% >0.05
 ≥60 and <70 159 50.9% 25.2% 20.8% 96.9%
 ≥70 and <80 146 54.1% 26.0% 14.4% 94.5%
 ≥80 29 40.0% 36.7% 13.3% 90.0%
Sex
 Male 155 58.1% 21.9% 16.8% 96.8% >0.05
 Female 236 45.3% 28.4% 20.3% 94.0%
Ethnicity
 White 255 52.2% 24.3% 18.4% 94.9% >0.05
 Asian 14 35.7% 28.6% 21.4% 85.7%
 African American 84 50.0% 28.6% 19.0% 97.6%

TABLE 2. - Correlation of Meibomian Gland Atrophy With Various MG Functional Measures
Functional Measure Spearman Correlation Coefficient (R) P
Meibum expressibility (n = 205) 0.22 0.001*
Meibum grade (n = 228) 0.103 0.123
Telangiectasia grade (n = 384) 0.014 0.787
Meibum expressibility + meibum grade (n = 197) 0.175 0.007*
*Statistically significant.

A subset of eyes (n = 236) had data available for gland atrophy and both key measures of MG function (meibum expressibility and meibum grade). In this subset, the percentage of eyes with moderate to severe functional changes (moderate or difficult meibum expressibility and/or meibum grade ≥2, n = 178/236; 75.4%) was statistically significantly greater than the percentage of eyes with MG atrophy ≥Grade1 (n = 220/236; 93.2%).

There was no significant difference in the prevalence of MG atrophy by grade in patients with a history of glaucoma, hypertension, autoimmune disease, or diabetes mellitus compared with those without such comorbidities (Table 3). Similarly, MG atrophy was similarly prevalent among smokers and nonsmokers.

Table 3: - Prevalence of Meibomian Gland Atrophy (Stratified by Severity Grade) in Patients With or Without Comorbidities (Glaucoma, Hypertension, Autoimmune Disease, and Diabetes Mellitus), Use of Cyclosporine, and History of Smoking
  N Meibomian Gland Atrophy P
Grade 1 Grade 2 Grade 3 Grade ≥1
History of glaucoma
 Yes 34 44.1% 38.2% 14.7% 97.0% 0.614
 No 348 50.9% 25.6% 18.7% 95.2%
History of hypertension
 Yes 262 48.5% 28.2% 19.1% 95.8% 0.486
 No 120 54.2% 23.3% 16.7% 94.2%
History of autoimmune disease
 Yes 28 64.3% 21.4% 7.1% 92.8% 0.530
 No 355 49.3% 27.0% 19.2% 95.5%
History of diabetes mellitus
 Yes 114 53.5% 22.8% 17.5% 93.8% 0.393
 No 268 48.9% 28.4% 18.7% 96.0%
History of dry eye diagnosis
 Yes 190 37.9% 35.3% 23.7% 96.9% 0.168
 No 194 62.9% 18.0% 12.9% 93.8%
History of cyclosporine use
 Yes 13 38.5% 46.2% 15.4% 100.0% 0.999
 No 371 50.9% 25.9% 18.3% 95.1%
History of smoking
 Yes 35 42.9% 42.9% 8.6% 94.4% 0.854
 No 221 48.0% 28.1% 19.0% 95.1%

Although the prevalence of MG atrophy was comparable among patients who had previously been diagnosed with DED versus those who were not, the severity of MG atrophy seemed to be higher in patients with a previous DED diagnosis compared with those without one (Table 3). The prevalence of MG atrophy (of any grade) was comparable in patients diagnosed with DED whether they had previously received DED treatment (cyclosporine or lifitegrast) or not (Table 3).

DISCUSSION

MGs play an important role in maintaining a healthy ocular surface. The quantification of meibum quality and expressibility is often used for evaluating MG function, and numerous studies have used these functional measures to determine the prevalence of MGD.13–17 Meibography offers direct observation of MG morphological architecture, independent of gland function, and has been shown to be useful in evaluating MG changes in MGD. Although it is less commonly measured, some authors have used structural data to determine MGD prevalence.4,8,18 In this study, we determined MGD prevalence based on evaluation of MG atrophy in a US-based population of patients presenting for cataract surgery evaluation.

Our findings suggest that MG atrophy is common in patients presenting for cataract surgery, with 95% of patients having some evidence of MG atrophy (grade ≥1) (Fig. 1). Although Cochener et al.8 reported 56% of patients with cataract to have at least grade 1 MG atrophy, Lin et al.19 reported ∼99% patients with cataract with MG atrophy of more than 10%. The differences between the findings of this study and those in the literature may be attributed to demographic differences in the study populations or to varying assessment approaches. For example, this study includes patients older than 50 years, whereas Cochener et al and Lin et al enrolled patients older than 40 years and older than 18 years, respectively. In addition, Lin et al evaluated atrophy in both eyelids compared with only lower eyelids in the study by Cochener et al. and the present study.

The current study explored the relationships between MG atrophy and several systemic/ocular conditions but found no association with hypertension, diabetes mellitus, autoimmune disease, or glaucoma (Table 3). Most previous studies have suggested an increased risk of MG atrophy in patients with hypertension,14,16,20 with 1 study documenting a lower risk.19 Similarly, in diabetic patients, several studies have demonstrated a moderate or high risk of MG atrophy16,19 and 1 study suggested no risk.14,19

It is widely accepted that functional changes in MGD precede structural alterations to the gland architecture.21 However, in the large subset of eyes for which we had complete functional data (meibum expressibility and meibum quality grade) available, the percentage of patients with MG atrophy (93.2%) was significantly higher than the percentage of patients with moderate/difficult meibum expressibility or meibum quality (grade ≥2) (75.4%), indicating that nearly 18% of patients with cataract had structural changes despite minimal or no functional changes.

This may suggest that structural changes to the glands sometimes precede functional alterations to meibum quality and expressibility. Alternatively, it may be that some older patients have age-related changes of the MGs resulting from a different mechanism than the commonly accepted mechanisms of ductal occlusion and hyperkeratinization. With aging, there is a decline in meibocyte differentiation and lipid synthesis, resulting in abnormal lipid secretion and gland dropout.22 This age-related decline in meibocyte differentiation and function leading to gland atrophy may also play a role in the development of MGD.23

In any case, our findings indicate that MGD with true MG structural changes would have been missed in some patients with good MG function, had meibography not been performed. Therefore, it is an important consideration to perform meibography in all patients with cataract, not just those with severe symptoms or poor MG function. Treating these patients may help slow the progression of MGD and prevent chronic symptoms because symptoms have been shown to worsen with cataract surgery alone in patients with known preexisting MGD.8,19 Optimizing ocular surface health before surgery and setting patient expectations to a realistic level can prevent postoperative dissatisfaction.

Decline in meibocyte differentiation may also occur in young, healthy individuals without corresponding clinical manifestations, as evident from the reports of gland dropout in apparently normal eyes.2,9,24 Environmental stress; neurogenic, hormonal, and dietary factors; excessive electronic screen use; and progenitor cell depletion have been documented to contribute to MG dropout and could be particularly implicated in gland dropout at younger ages.25,26 As such, meibography should be performed as an integral part of MGD or ocular surface disease (OSD) assessment, regardless of patient age or gland function.

It may be assumed that MG atrophy is more likely to be found in known cases of DED. However, in this study, although severe (grade 3) atrophy was more likely in patients with a DED diagnosis, the overall rate of gland atrophy (≥grade 1) was similar whether previously diagnosed with DED or not (Table 3). More importantly, among patients with no previous history of DED diagnosis, 18% had moderate and 13% had severe MG atrophy (Table 3). Had preoperative evaluation of the MG structure, such as with infrared meibography, not been performed in these patients, MGD may not have been identified, limiting the opportunity for treatment and the ability to accurately plan for cataract surgery.

Assessment of both MG morphology and function may have relevance in surgical decision making and IOL selection, particularly in those having a specific refractive visual goal or planning to get a multifocal or toric IOL. If MG status is not optimal, these patients should be recommended to undergo MGD treatment before surgery. A recent study has demonstrated that a significant proportion of eyes scheduled to undergo cataract surgery showed changes in astigmatism magnitude and axis of orientation after vectored thermal pulsation treatment, which led to changes in their surgical management plan.7 Thermal pulsation treatment has been demonstrated to be effective in improving MG function.27–29 Recent studies have shown that vectored thermal pulsation/Lipiflow treatment conducted before cataract surgery is an effective intervention for alleviating blockage of MGs and relieving MGD symptoms.30,31 As such, patients may be more satisfied when cataract surgery is performed after achieving better ocular surface health after thermal pulsation treatment.

More than half of the patients in this study had mild MG atrophy. Thermal pulsation treatment in these patients may potentially improve patient satisfaction after premium IOL implantation. Although patients with moderate or severe MG atrophy may also benefit from the thermal pulsation treatment, thorough counseling is imperative for those who do not demonstrate improvement in gland function even after treatment. If considering presbyopia-correcting IOLs, these patients should be duly informed of the risk of dysphotopsia postoperatively. In extreme cases, patients may be dissuaded from getting a premium IOL.

With age, MG acinar epithelial cells tend to atrophy; as such, aging is a well-known risk factor for MGD.32 A positive correlation between age and MG loss/atrophy has been documented previously.18,33,34 However, in this study, there was no correlation between MG atrophy and age (Table 1). This may be because the relatively younger subjects of the study cohort (age range 50–90 years) may be exposed to higher screen time or contact lens wear than those who were relatively older.26 It is also possible that the older patients in the present cohort might have overall healthier lids and lenses because they developed cataract at an older age. Larger studies with representative age populations could perhaps better elucidate the contribution of other contributing factors to age-related MG architecture changes.

It is widely accepted that once MGs have atrophied, these structural changes are permanent, and the glands cannot be reactivated or regenerated. However, there is some recent evidence to suggest that vectored thermal pulsation treatment may improve the MG structure in ∼70% eyes.35 Longitudinal studies may help better understand changes in the MG architecture over time and associated risk factors.

The retrospective nature of this study, as well as the fact that it was a single-center study, can be considered potential limitations. Future studies with a prospective study design and larger data set are needed to validate these findings. Grading of gland atrophy was conducted in a semiquantitative fashion, based on a percentage of gland loss. Although this or similar methodologies have been used by other researchers, estimation of gland counts is a limitation in all such studies.8,12,19

In conclusion, MG atrophy is common in patients presenting for cataract surgery evaluation, indicating that MGD-associated DED is underdiagnosed. Routine use of meibography to evaluate gland structure during preoperative screening in cataract surgery patients, in addition to assessment of gland function, may facilitate the timely and effective diagnosis and treatment of MGD, leading to better surgical decision making.

ACKNOWLEDGMENTS

Raman Bedi, MD (IrisARC - Analytics, Research & Consulting, Chandigarh, India), and Jan Beiting (Wordsmith Consulting, Cary, NC) provided research, statistical, and editorial assistance in the preparation of this manuscript.

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Keywords:

meibomian gland atrophy; dry eye disease; meibomian gland dysfunction; meibography

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.