Looking out the airplane window at the mountainous Colorado landscape below, the entire forest is visible. The individual trees blend into one velvet-like expanse to create a full forest. I paint you this picture to stress that it’s important to see the scene as a forest rather than focusing on the individual trees, as the saying goes. So, is meibomian gland dysfunction (MGD) the forest or is it the tree?
In my opinion, the reason dry eye has so many vagaries associated with diagnosis and management is because of our incomplete understanding of MGD and the cause-and-effect relationship of the condition. MGD is most likely both forest and tree—both the cause and the effect. Time—or the temporal pattern of MGD—may be a critical factor in teasing out these fundamental differences.
Unveiling the Report
This past March, the International Meibomian Gland Dysfunction workshop published its report in Investigative Ophthalmology and Visual Science (“The International Workshop on Meibomian Gland Dysfunction,” Special Issue, March 2011).1 Undertaken by the Tear Film & Ocular Surface Society (TFOS), this publication marks the first time IOVS has dedicated a special issue to a single report of this type.
Similar to the breakthrough nature of the TFOS-authored report of the International Dry Eye WorkShop (DEWS) that was published in The Ocular Surface in 2007, we may be on the cusp of similar game-changing news for the subset of dry eye conditions involving MGD. Complete or partial translations of this MGD report will be offered in numerous languages and will be distributed around the world.
Global Consensus
In late 2008, TFOS initiated a workshop on MGD using the DEWS format as a guide. More than 50 international experts participated in the effort, which took place over a two-year period. The process was sponsored generously through industry support via unrestricted grants to TFOS, allowing volunteers to come together to create a consensus overview of the field.
In addition to an exhaustive international literature-based review of the salient clinical, translational and basic research, emerging concepts such as a new diagnostic and management algorithm were also included. The report that followed is the most current, definitive, global consensus summary of the meibomian gland in health and disease.
The following summary is excerpted from “The International Workshop on Meibomian Gland Dysfunction: Executive Summary.”2 I encourage you to visit the TFOS website (
www.tearfilm.org) to read the complete published report.
Leading Cause of Dry Eye
MGD may well be the leading cause of dry eye disease throughout the world. Although this condition influences the health and well-being of millions of people, there has not been a global consensus on the definition, classification, diagnosis or therapy of MGD. Thus, the aim of the workshop was to use an evidence-based approach to develop a contemporary understanding of the definition and classification of MGD; to assess methods of diagnosis, evaluation and grading of severity of MGD; to develop recommendations for the management and therapy of MGD; and to create a summary of recommendations for future research in MGD.
Definition and Terminology
Due to the limited studies on treatments for MGD and MGD-related dry eye, the MGD Workshop committee suggests the following main priorities in future clinical trials in MGD:9
The committee proposed the following definition of MGD: “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.”3
Future Trials
Part of the challenge with previous clinical research and publications in this area was inconsistency in terminology. To unify the field, the workshop had to review and agree upon its terminology. First, the term “dysfunction” was used because the overall function of meibomian glands is altered. The term “diffuse” was chosen because the disorder involves most of the meibomian glands, rather than isolated glands (e.g., hordeola).
Obstruction of the meibomian gland orifices, terminal ducts and qualitative and/or quantitative changes in meibomian gland secretions were identified as the most prominent aspects of MGD. In addition, subjective symptoms of eye irritation were included in the definition because the symptoms are of greatest concern to the patient and often the clinician. Improvement in patient symptoms is the major goal of MGD treatment.
Additional terms warranting discussion include “posterior blepharitis,”often referred to as synonymous with MGD. Posterior blepharitis is a term used to describe inflammatory conditions of the posterior lid margin, of which MGD is only one cause. In its earliest stages, MGD may not be associated with clinical signs characteristic of posterior blepharitis. The role of inflammation in the etiology of MGD is controversial and uncertain.
In early stages of MGD, patients may be symptomatic, but alternatively they may be asymptomatic and termed subclinical. As MGD progresses, additional symptoms develop as well as lid margin signs, such as changes in lid margin redness/edema and meibum expressibility and quality. At this point, MGD-related posterior blepharitis is said to be present. Ultimately, MGD can lead to alterations of the tear film, symptoms of eye irritation, inflammation and dry eye.
Classification
The workshop proposed that MGD should be classified into two major categories based on meibomian gland secretion: low delivery states and high delivery states. Low delivery states are further classified as hyposecretory and obstructive, with cicatricial and non-cicatricial subcategories.
Hyposecretory MGD describes the condition of decreased meibum delivery due to abnormalities in meibomian glands without remarkable obstruction. Importantly, obstructive MGD is due to terminal duct obstruction. In the cicatricial form, the duct orifices are dragged posteriorly into the mucosa, whereas these orifices remain in their normal position in non-cicatricial MGD.
Anatomy, Physiology and Pathophysiology
• Anatomy. The meibomian glands are large sebaceous glands located in the tarsal plates of the eyelids, and their job is to secrete the lipids critical to maintaining the stability of the tear film. Each meibomian gland consists of multiple secretory acini containing meibocytes, lateral ductules, a central duct and a terminal excretory duct that opens at the posterior lid margin.
There are more glands in the upper lid; the relative functional contribution of the upper and lower lid glands to the tear film and the method of lipid delivery to the tear film remain to be determined.4
• Physiology. The glands are regulated by androgens, estrogens, progestins, retinoic acid and growth factors, and possibly by neurotransmitters.
The exact components of meibum include a complex mixture of various polar and non-polar lipids containing cholesterol and wax esters, diesters, triacylglycerol, free cholesterol, free fatty acids and phospholipids, yet some of the differences in meibum between normal and MGD patients have yet to be fully characterized on a molecular level.
In contrast to the overall thickness of the tear film (roughly 3µm to 40µm), the tear lipid layer thickness is 15nm to 160nm. If you assume the tear film thickness is 4µm and the lipid layer thickness 100nm, the lipid layer comprises 100nm/4000nm or 2.5% the total tear thickness. Tear film lipids also appear to be essential for ease and comfort in contact lens wear, despite forming deposits on lenses. Contact lens wear itself may disrupt the meibomian glands and/or lipid layer and lead to tear film evaporation and ocular surface discomfort.5
• Pathophysiology. The primary cause of MGD is terminal duct obstruction with thickened opaque meibum containing keratinized cell material. This obstruction is due to hyperkeratinization of the ductal epithelium and increased meibum viscosity. The obstruction may lead to pressure within the gland, meibocyte atrophy, gland dropout and low secretion.
The end result of MGD is reduced availability of meibum to the lid margin and tear film, and the resultant instability of the tear film, possibly potentiating bacterial growth on the lid margin, evaporative dry eye, ocular surface inflammation, damage and symptoms.5
Epidemiology and Associated Risk Factors
• Epidemiology. The reported prevalence of MGD varies widely, and studies specific to MGD are lacking. In the existing studies, a striking observation is that the prevalence of MGD appears to be much higher in Asian populations (approaching 65% depending on the method of classification).6 Further studies of prevalence, incidence, natural history and impact on quality of life are needed.
• Risk factors. Multiple associated factors have been identified, including anterior blepharitis, contact lens wear, Demodex mites, androgen deficiency, menopause, aging, Sjögren’s syndrome, higher cholesterol levels, psoriasis, atopy, rosacea, hypertension and benign prostatic hyperplasia (BPH). In addition, medications used to treat BPH, antiandrogens, postmenopausal hormone therapy (e.g., estrogens and progestins), antihistamines, antidepressants and retinoids have also been identified. Omega-3 fatty acids may be protective.6
Diagnosis and Management
The diagnosis and management of MGD is of greatest interest to the clinician. The diagnosis of MGD—whether in isolation or associated with ocular surface damage or dry eye—should be viewed in the context of diagnosing any ocular surface disease in a medically oriented ocular surface examination.
• Diagnostic tests. Include gland expression to evaluate the quality and quantity (availability) of meibomian gland secretions. Digital pressure on the lower lid for approximately 15 seconds in duration with a slight rolling upward of the cotton swab or fingertip usually results in expression of meibomian gland secretions. The glands can then be evaluated for expressibility and meibum quality.7
A diagnosis of MGD may require that the patient be further assessed for symptoms, lid morphologic signs and ocular surface damage (staining). The MGD Workshop has proposed a staging of disease, from asymptomatic to severe.
• Management and therapy. Evidence-based principles guided the preparation of the MGD Workshop report. The same evidence guidelines were used in the DEWS process and are a modification of the American Academy of Ophthalmology’s Preferred Practice Patterns guidelines. As such, the new diagnosis and management algorithm presented in the report is an assimilation of the clinical research published to date.
Treatment of MGD varies greatly among eye care providers, and data to support any one treatment over the other is limited. Current standard of care includes warm compress therapy, the consideration of omega fatty acid supplements, topical azithromycin, artificial lubricants (preferred non-preserved for frequent use), topical emollient lubricant or liposomal spray, oral tetracyclines, meibomain gland therapeutic expression, or topical cyclosporine for cases with concurrent significant corneal staining/aqueous dry eye.8
MGD is an extremely important condition, conceivably underestimated and very likely the most frequent cause of dry eye disease. MGD may also have some association with aqueous-deficient dry eye. Therefore, a complete dry eye examination should include symptom evaluation, clinical assessment of the meibomian glands, meibomian gland expressibility and evaluation of the quality of meibomian gland secretions. Co-existing dry eye should be evaluated through assessment of tear film instability and ocular surface staining.
We hope that this report will motivate clinicians to look at the meibomian glands more closely, as well as to inspire future clinical and translational research with the ultimate goal of improving care of MGD and dry eye patients around the world.
Dr. Nichols is an associate professor at the Ohio State University College of Optometry, in Columbus, Ohio. She lectures and writes on ocular surface disease and currently chairs the International Meibomian Gland Workshop sponsored by the Tear Film and Ocular Surface Society.
She is a paid consultant to Allergan, Alcon, Inspire, Occulogix (TearLab) and Pfizer, and has NIH funding to study dry eye in postmenopausal women.
1. Nichols KK. The International Workshop on Meibomian Gland Dysfunction: Introduction. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1917-21.
2. Nichols KK, Foulks GN, Bron AJ, et al. The International Workshop on Meibomian Gland Dysfunction: Executive Summary. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1922-9.
3.Nelson JD, Shimazaki J, Benitez-del-Castillo J, et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Definition and Classification Subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1930-7.
4. Knop E, Knop N, Millar T, et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Anatomy, Physiology and Pathophysiology of the Meibomian Gland. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1938-78.
5. Green-Church K, Butovich I, Willcox M, et al. The International Workshop on Meibomian Gland Dysfunction: Report on the Subcommittee on Tear Film Lipids and Lipid-Protein Interactions in Health and Disease. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4): 1979-93.
6. Schaumberg D, Nichols J, Papas E, et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommitee on the Epidemiology of, and Associated Risk Factors for, MGD. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4): 1994-2005.
7. Tomlinson A, Bron A, Korb D, et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Diagnosis Subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4): 2006-49.
8. Geerling G, Tauber J, Baudouin C, et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Management and Treatment of Meibomian Gland Dsyfunction. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4): 2050-64.
9. Asbell P, Stapleton F, Wickström K, et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Clinical Trials Subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4): 2065-85.
