Latest evidences on meibomian gland dysfunction diagnosis and management
Introduction
Even though Meibomian gland dysfunction (MGD) can be considered the worldwide leading cause of dry eye disease throughout the world [1], affecting millions of people, before the 2011 International Workshop on Meibomian Gland Dysfunction (IWMGD) [1] there was no consensus on the definition, classification, diagnosis, and treatment of this disease. (see Table 1, Table 2, Table 3, Table 4, Table 5, Table 6)
After a comprehensive review of clinical textbooks and the scientific literature, the Definition and Classification Subcommittee finally stated that “Meibomian gland dysfunction is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. This may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease”.
MGD presents as a heterogeneous complex condition, mainly categorized into low-delivery meibum and high-delivery meibum. Low-delivery states are further differentiated into hyposecretory, where there is a decreased delivery in absence of substantial obstruction, or obstructive, with cicatricial and noncicatricial subcategories. High delivery states, in which a large amount of meibum is released in response to pressure on the tarsus, are classified as primary/idiopathic or secondary to seborrheic dermatitis or acne rosacea [2].
In a recent article Baudouin et al. propose a double vicious pathophysiological circle where meibomian gland alterations provide an entry point into both MGD and DED loops. Meibomian gland blockage, gland dropout and/or atrophy result in meibum stasis and microbial proliferation, self-sustaining the MGD vicious circle. Tear-film instability associated to MGD would play as an entry point in DED vicious circle, leading to hyperosmolarity and inflammation, thus resulting in further MG keratinization and subsequently contributing to the amplification of both the vicious circles [3].
In the absence of a single gold-standard diagnostic test, clinical examination plays a key role in the diagnosis of MGD before any imaging is performed. Both the expressibility and the consistency of the meibum are altered, changing from a cloudy fluid to an opaque, thickened pastelike substance. Changes in lid morphology can be assessed through slit-lamp examination and include hyperkeratinization, thickening and rounding of the lid margin, telangiectasia, and increased vascularity. The plugging of the meibomian orifices caused by the obstruction of the terminal ducts and the extrusion of glands’ excreta are characteristic of the disease. Alterations in the location and morphology of the mucocutaneous junction, such as anteroplacement, retroplacement, mucosal absorption, and epithelial ridging between gland orifices, can be observed. Cystoid dilatation of the ducts, concretions within acini and chalazia can finally occur [4].
The recent imaging revolution in the field of ocular surface is shifting the leading clinicians' and researchers' focus on meibography (widely used in clinical practice and as a biomarker in clinical research) and on potentially useful technologies such as optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM) [[5], [6], [7]].
The growing interest in MGD is providing mounting evidence of the effectiveness and safety of the management of this condition. However, in spite of great efforts from the IWMGD to develop a therapeutic algorithm [8] based on data and disease progression [8], MGD treatment is still inconsistent among eye care providers in different countries, and the most effective use of each therapeutic approach still needs to be assessed.
Several factors limit the evaluation of the available literature on MGD. These include heterogeneous terminology, very different levels of evidence and quality of published studies, varied and sometimes conflicting diagnostic criteria, and issues related to the differentiation between MGD and DED.
We have attempted to overcome these limitations, in order to highlight the latest published evidences on MGD diagnosis and treatment.
Section snippets
Selection of articles for review
An initial scientific literature search was conducted last on April 1, 2020 using the PubMed database.(see Table 7, Table 8, Table 9, Table 10, Table 11, Table 12, Table 13)
Articles were retrieved, and the reference list of each article was reviewed to identify other relevant papers. A secondary literature search was finally conducted in the Embase database.
Based on a priori established criteria, we screened the papers sequentially with the following order: titles, abstracts, and full-text. Two
Latest evidences on diagnosis
The articles that made it to the final selection focused on imaging techniques such as Meibography, Optical Coherence Tomography and in vivo confocal microscopy, with an emphasis on the key role of morphological evaluation in MGD diagnosis, as shown in Fig. 2. A final section was dedicated to the application of Artificial Intelligence (AI) to MGD diagnosis.
Latest evidences on treatment
We chose to include in our review medical treatments and procedures of proven efficacy and safety, obtained from randomized clinical trials.
Antibiotics, including macrolides and tetracyclines, steroids, cyclosporine, essential fatty acids, diquafosol, intraductal meibomian gland probing, electronic heating devices, intense pulsed light therapy and electrotherapy are described in the following paragraphs.
Discussion
Advancements in medical imaging technology have led to faster and less invasive methods for MGD evaluation. Two-dimensional images did not allow to discriminate between the absence of the gland and its altered function and have been therefore compared to tridimensional reconstructions, where ultrastructural details of the biological tissue allows the direct quantification of pathophysiological processes. The development of validated, repeatable, and automatic morphological features assessment
Declaration of competing interest
None for any of the authors.
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Cited by (32)
Latest developments in meibography: A review
2022, Ocular SurfaceCitation Excerpt :Many other reviews have described the evolution of various meibography techniques [13–18]. A few more recent ones focused more on diagnostic relevance of meibography findings [3,19,20]. Arita [3] presented a Japanese perspective on non-contact meibography with the main focus on changes to Meibomian glands associated with various ocular surface diseases and conditions including aging and contact lens (CL) wear.
Morphological characteristics of Meibomian Glands and their Influence on Dry Eye disease in contact lens wearers
2022, Ocular SurfaceCitation Excerpt :Each of these scales classify ‘no atrophy’ as a 0 grade and ‘severe atrophy’ with the highest-grade number. Subjective grading of MG atrophy has been shown to be sensitive and specific for predicting MGD, though there is limited knowledge related to how MG atrophy is related to predicting general DED [19]. MG tortuosity has likewise garnered interest in recent years, with greater numbers of tortuous glands representing worse MG health [12,25,26].
Artificial intelligence in dry eye disease
2022, Ocular SurfaceCitation Excerpt :Reduced secretion of meibum due to a reduced number of functional meibomian glands and/or obstruction of the ducts is a major cause of evaporative DED and MGD. Meibography is a common technique for diagnosing MGD [80]. Classification of meibomian glands using meibography is routine for experienced experts, but this is not the case for all clinicians.
Quantitative analysis of morphological and functional features in Meibography for Meibomian Gland Dysfunction: Diagnosis and Grading
2021, eClinicalMedicineCitation Excerpt :Conversely, for the lowest MGD severity (level 1), the GA was slightly increased, which may be a result of MG dilation and thickening. Increased MGs thickness was also observed to be inversely correlated with meibum expression and considered to be a compensatory response to gland loss and increased meibum demand [36]. Dilation of secretory acini could be part of the same process, as a result of the expansion of accumulated and inspissated debris within the acini observed in previous studies [23,37,38].
Application status and progress of artificial intelligence in dry eye associated with meibomian gland dysfunction
2024, Chinese Journal of Experimental Ophthalmology