A supplement to Sponsored by Meibomian gland dysfunction From theory to daily ophthalmic practice Introduction he term ‘Meibomian Gland Dysfunction’ (MGD) was first used by Korb and THenriquez in 1980,1 and has given impetus to the study of the disease. According to some reports, up to 70% of people2 suffer from MGD. Given the prevalence of the condition, which is the major cause of evaporative dry eye and possibly of dry eye overall,3,4 MGD therefore represents an important disorder in need of management. The assessment, diagnosis and management of the condition have been inconsistent in the past, due to the lack of a clear definition and classification of MGD. To combat this, the Tear Film and Ocular Surface Society (TFOS; www.TearFilm.org) convened the International Workshop on Meibomian With contributions from Gland Dysfunction, involving an international group of clinicians and research Professor Anthony J Bron, FRCS of scientists who reviewed the causes, pathophysiology, diagnosis and treatment Nuffield Laboratory of Ophthalmology, of the condition. Over a two year period, and with sponsorship from several University of Oxford, UK, member of pharmaceutical companies, including Laboratoires Théa, the Workshop has the steering committee of the TFOS now produced a definitive, evidence‑based assessment of MGD, which can be International Workshop. regarded as a milestone event. At the 2011 EVER Congress in Crete, Greece, Laboratoires Théa held a Professor Erich Knop, Ocular Surface symposium to present some of the information from the workshop as well as Center Berlin, Department for Cell and ways to put the treatment recommendations into daily ophthalmic practice. In Neurobiology, Center for Anatomy, this supplement we will present some of the highlights of this symposium. Charité–Universitätsmedizin Berlin, Germany; Visit. Prof. Fac. of Medicine, A collaborative approach Juntendo University, Tokyo. Chair of the TFOS is a non‑profit organization dedicated to advancing the research, literacy Anatomy, Physiology and Pathophysiology and educational aspects of the scientific field of the tear film and ocular surface of the Meibomian Gland subcommittee of throughout the world. As part of this work, TFOS sponsors the International the TFOS International Workshop Workshop on Meibomian Gland Dysfunction, a collaborative project researching the subject of MGD. Professor Gerd Geerling, Department “Of course, industry support was important for the success of the workshop of Ophthalmology at Heinrich‑Heine and Théa has played a prominent role. Recently, Théa supported the University in Düsseldorf, Germany. Chair dissemination of the conclusions of the workshop across Europe and of the Management and Therapy of MGD arranged translations into 10 different languages (French, German, Italian, subcommittee of the TFOS International Spanish, Portuguese, Dutch, Polish, Turkish, Russian and Greek) helping Workshop everyone to understand the disease better,” according to Professor Anthony Bron. Professor Zbigniew Zagórski, PhD, MD, “The workshop’s intention,” he continued, “was to conduct an evidence‑based Professor and Chairman Emeritus, Tadeusz evaluation of meibomian gland structure, function and dysfunction, devise Krwawicz Chair of Ophthalmology, a contemporary definition and classification of MGD, assess methods of Medical University, Lublin, Poland. diagnosis and grading, appraise clinical trial design, review the literature and make recommendations for management and therapy.” The final reports of Doctor Serge Doan, MD, Department the International Workshop4–12 were published earlier this year in Investigative of Ophthalmology, Bichat Hospital and Ophthalmology & Visual Fondation A. de Rothschild, Paris, France. Sciences (IOVS). The Figure 1: Stagnated meibomian secretions. separate parts of this Courtesy of Prof. Benitez Del Castillo. Professor Pierre-Jean Pisella, TFOS MGD report have Department of Ophthalmology at the immediately become the Francois Rabelais University, Tours, most requested papers France. in the all time best list of IOVS, which indicates the utmost importance of MGD and the respective very high interest of Sponsored by the ophthalmological community. 2 Ophthalmology Times Europe December 2011 MGD report highlights: Theory Professor Erich Knop re‑stated the definition of MGD developed lids, in the absence of tarsal conjunctival scarring. There is also at the workshop: a ‘hypersecretory’ or ‘high delivery’ state in which light pressure on the eyelid over the glands expresses copious meibum Definition discharge. MGD most frequently occurs in the low delivery “Meibomian Gland Dysfunction (MGD) is a chronic, form, and is most often caused by obstructive disease (more diffuse abnormality of the meibomian glands, commonly specifically, by obstructive non-cicatricial disease). characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. Anatomy, physiology, pathophysiology and epidemiology It may result in alteration of the tear film, symptoms of Understanding the anatomy of the meibomian gland is key to eye irritation, clinically apparent inflammation, and ocular understanding MGD. The glands themselves are single, large and surface disease.”5 sebaceous but are not directly associated with hair follicles. They are located in and almost completely fill, the lower and upper “That is the first definition of MGD and derived through global tarsal plates of the eyelids. consensus,” explained Prof. Erich Knop. “To go a bit more into Meibomian glands contain several acini, where the secretion detail, when MGD is stated to be diffuse, it means it does not of the meibomian oils (meibum) is performed by the secretory affect all of the roughly 30 single meibomian glands that we have cells (meibocytes). These acini are connected by lateral ductules along each lid margin, but usually only some of them at varying to a main, long, straight duct, which runs through the centre of numbers and degrees.” the gland. The meibum is then delivered through an excretory “Obstruction of the terminal duct and orifice due to duct onto the posterior part of the lid margin. “You can imagine hyperkeratinization is one of the important factors: the secretum (meibum) cannot get out and is stuck inside the gland. Another contributing factor is qualitative and/or “If you diagnose MGD too late or treat quantitative changes in the glandular secretions. Both of it too late, then the gland may already these — the hyperkeratinization and the qualitative change in secretion — result in obstruction,” he added. be burnt out and so you’ve lost your therapeutic options.” Classification “Terminologically, as originally defined by Foulks and Bron in Professor Erich Knop 2003,13 one important step in the classification is to differentiate between disease and dysfunction,” said Prof. Knop. ‘Meibomian that such a complicated gland structure gives rise to a lot of gland disease’ is, in this respect, the correct term to use for a potential pathological insults, which is in fact the case in MGD,” broad range of disorders, including congenital, neoplastic or explained Prof. Erich Knop who is the chair of the MGD Workshop acute conditions, among others. “However,” he added, “the Subcommittee for Anatomy, Physiology and Pathophysiology of dysfunction, specifically refers to a chronic, usually obstructive, the meibomian glands. condition of the Meibomian glands. We have to differentiate Physiologically, it is necessary to differentiate between the between low and high delivery states, of which the low delivery actual secretion of oils, which takes place in the acini (mostly a states are most prevalent.” long distance from the posterior lid margin surface), and their The division of MGD into low and high delivery states has delivery. The delivery is out of the gland, through the excretory further sub‑classifications. The low delivery state has two forms: duct, onto the lid margin. The secretion results from the constant hyposecretory and obstructive. The MGD resulting from systemic division and maturing of cells that eventually disintegrate to form retinoid toxicity would be an example of a hyposecretory state. the meibomian oils, but the delivery needs some help, which is More often, obstructive MGD is encountered and this may exist in given by the contractile forces of the orbicularis and the muscle cicatricial and non‑cicatricial forms. The cicatricial form occurs, of Riolan during the blink. That these muscles play a role is in particular, in the presence of cicatricial conjunctival disease indicated by the fact, that blinking has a significant impact on the such as Stevens Johnson syndrome and trachoma but cicatricial delivery of meibum. A lack of blinking leads to a deficiency of oil and non‑cicatricial changes may also occur together in the same delivery onto the lid margin and, in reverse, intentional forceful blinking leads to increased oil on the lid margin and in the tear film lipid layer and hence represents a therapeutic option in “You can imagine that such a incipient MGD, noted Prof. Knop. Hormones are a major driving force for the meibomian glands: complicated gland structure gives rise androgens are generally a positive stimulus for the differentiation to a lot of pathological insults, which and function of the ocular surface tissues and glands, whereas estrogens are negative for gland function. is in fact the case in MGD.” This could be relevant to the greater prevalence of MGD in Professor Erich Knop women