Report elucidates meibomian gland dysfunction definition, diagnosis

An international workshop recommends an evidence-based approach to classifying and grading the disease and distinguishing it from dry eye syndrome.

A report defined meibomian gland dysfunction and recommended methods of diagnosis, treatment and clinical trial design.

The Tear Film and Ocular Surface Society announced results of the International Workshop on Meibomian Gland Dysfunction. The report, which took more than 2 years to complete, incorporated evidence-based data gathered by more than 50 international researchers.

The report is a roadmap for clinical treatment and research for meibomian gland dysfunction (MGD), Kelly K. Nichols, OD, MPH, PhD, the corresponding author, said in an interview with Ocular Surgery News.

“It was more of a process rather than a single meeting that occurred,” Dr. Nichols said. “The report provides a blueprint for what should happen to move the field forward in the future.”

Penny A. Asbell, MD, FACS, MBA, OSN Contact Lenses Section Editor and chair of the workshop’s subcommittee on design and conduct of clinical trials, said there was a paucity of definitive information on the nature and specificity of MGD, less than the evidence on other types of ocular surface disease such as dry eye.

“If you look at the clinical trial data to date, it often is not clear if the trial is evaluating lid disease alone or lid disease in conjunction with dry eye disease,” Dr. Asbell said. “I think the whole conundrum of understanding these conditions and their interaction needs to be further explored.”

The report was published in a special issue of Investigative Ophthalmology & Visual Science.

Dr. Nichols and fellow committee members defined MGD in the report.

“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. It may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation and ocular surface disease,” the authors wrote.

The group classified MGD into two major types based on meibomian secretion: low-delivery states, considered to be the most common cause of MGD, and high-delivery states. MGD spurs changes in the tear film, symptoms of eye irritation and inflammation, and dry eye, the authors said.

“We previously did not have a definitive definition for meibomian gland dysfunction,” Dr. Nichols said. “There have been classification systems, and what we’ve presented here is a revised classification scheme.”

A standard definition is essential for epidemiologic investigation of disease etiology, clinical presentation and progression, Dr. Nichols said.

“We found that across many different papers, both clinical and basic research, there was a lack of terminology that was consistent,” she said. “It is difficult moving a field forward because if you’re not talking the same words, using the same language, then you don’t know if you’re comparing apples to oranges or apples to apples. The report sets the appropriate framework.”

Diagnosis and treatment

The workshop devised a diagnosis and treatment algorithm that combines management of MGD and dry eye.

“There previously has not been an algorithm in existence for MGD,” Dr. Nichols said. “This is a new addition to the literature and essentially something that is very approachable from a clinical utility standpoint for clinicians in terms of trying to manage MGD in context of dry eye disease, because we felt that it was very difficult to separate out dry eye from MGD and try to treat them as two distinct conditions.”

The workshop recommended a two-tiered approach to the diagnosis of MGD-related dry eye. First, normal subjects should be distinguished from those with dry eye of any type. Second, a differential diagnosis of MGD-related evaporative dry eye and aqueous-deficient dry eye should be performed, the authors said.

“Some of the dry eye prevalence studies that have identified patients with dry eye using symptoms very likely include a large percentage of patients who have meibomian gland dysfunction,” Dr. Nichols said. “We don’t really know, but the line is blurred between the two.”

The workshop also devised a disease staging system that ranks MGD grades and symptoms and factors in ocular comorbidities that may require concurrent management.

Clinical trial design

New norms of clinical trial design are necessary to advance research and develop effective treatments for MGD, Dr. Asbell said. She chaired the workshop’s subcommittee on design and conduct of clinical trials.

The subcommittee reviewed 26 published papers identified as clinical trials on MGD. Many of these papers offered no clear definitions or distinctions between MGD and dry eye, Dr. Asbell said.

Clinical trial designs allow for generation of progressively advanced levels of evidence, she said.

“Typically, the highest level of evidence is a randomized controlled trial where the participants are masked,” she said. “Below this highest level are other levels of evidence, such as cohort data, where findings on a group of people are reported. At the bottom of the evidence tree are case reports. However, case reports have an important role to alert us of areas that require more extensive research, but they rarely can supply definitive information on diagnosis or treatment.”

An appropriate starting point for MGD research would be an observational trial that examines signs and symptoms of MGD, comparing MGD subjects with age-matched controls. In addition, long-term surveillance would provide key information on the natural history of the disease, how it first presents and change in MGD over time. – by Matt Hasson and Courtney Preston

Reference:

• Nichols KK, Foulks GN, Bron AJ, et al. The International Workshop on Meibomian Gland Dysfunction: Executive Summary. Invest Ophthalmol Vis Sci. 2011;52(4):1922-1929.

• Penny A. Asbell, MD, FACS, MBA, can be reached at Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 118, New York, NY 10029; 212-241-7977; email: penny.asbell@mssm.edu.
• Kelly K. Nichols, OD, MPH, PhD, can be reached at Ohio State University College of Optometry, 338 W. 10th Ave., Columbus, OH 43210; 614-688-5381; email: knichols@optometry.osu.edu.
• Disclosures: Dr. Asbell has financial or consulting relationships with Aton Pharma, Bausch + Lomb, Johnson & Johnson, Merck, Otsuka, Pfizer and Vindico Medical Education. Dr. Nichols has financial relationships with Alcon, Allergan, Inspire, Pfizer and TearLab.

All of us in the ophthalmic and optometric communities owe a debt of gratitude to TFOS and the Workshop on Meibomian Gland Dysfunction for their report. The Workshop has brought definition and classification to this often misunderstood, underdiagnosed and undertreated condition. The report has used evidence-based medicine and a transparent review process to suggest therapies for each level of disease. The Workshop has also given our communities much-needed norms for clinical trial design, such that we can evaluate potential pharmacological and mechanical interventions for MGD.

– Marguerite B. McDonald, MD
OSN Refractive Surgery Board Member
Disclosure: Dr. McDonald is a consultant for Inspire Pharmaceuticals.