Monday, April 4, 2011

International Workshop on MGD

For those of you who are serious about following MGD research, IOVS' special issue covering the International Workshop is a must-read.

Click here for the contents page of IOVS special issue.

Just to give you an idea of the scope, here's an excerpt from Kelly Nichols' excellent Introduction:


There are rare occasions in a field of science when significant advances occur in leaps and bounds, rather than in small, deliberate steps. This moment is imminent in the field of meibomian gland dysfunction (MGD)—and therefore in dry eye disease. The goals of the International Workshop on Meibomian Gland Dysfunction were twofold: first, to develop a consensus understanding of the meibomian gland in health and disease; second, to disseminate the knowledge broadly to further the field.

Over the past several years, although the body of knowledge about dry eye has been expanding, it has become clear that significant detail and direction relative to the impact of the meibomian gland in dry eye have been lacking. The Tear Film and Ocular Surface Society (TFOS;, a nonprofit organization, launched the International Workshop on Meibomian Gland Dysfunction ( in conjunction with generous industry sponsors that supported the workshop process through unrestricted grants, allowing volunteers to come together to plan, execute, translate, and present the findings of the workshop at a variety of meetings worldwide.


International workshops, such as the Dry Eye Workshop (DEWS) and this workshop on MGD, provide a consensus overview of the field as a snapshot in time. In addition to an exhaustive international literature–based review of the salient clinical, translational, and basic research, new concepts—often assimilated through the process of refining the reports—are also included here. Thus, this report is the most current, definitive summary of the meibomian gland in health and disease. As such, the objectives defined by the Steering Committee were as follows:

- to develop a contemporary understanding of the definition and classification of MGD;

- to conduct an evidence-based evaluation of meibomian gland structure and function in health and disease;

- to critically assess the structure of meibomian lipid and the interaction of the secreted lipid with additional components of the tear film;

- to evaluate the prevalence and associated risk factors for MGD;

- to assess methods of diagnosis, evaluation, and grading of severity of MGD;

- to evaluate existing recommendations and provide a diagnostic/therapeutic algorithm for the management and therapy of MGD;

- to evaluate existing clinical trials of pharmaceutical interventions for the treatment of MGD and provide recommendations for future clinical trial design; and

- to create an executive summary of recommendations for future research in MGD.

Newsblurb: Hm, which part was news?

Dry Eye Syndrome Affects More Women Than Men
by Prevent Blindness America, March 30, 2011

Well, the headline certainly wasn't news. And most of the rest of the article has the same-old warmed over advice so I won't quote it all here, but there were a few interesting tidbits:

..Women are also more likely to develop Dry Eye. Approximately 6 million have moderate to severe symptoms of dry eye syndrome, as compared to 3 million men, according to the National Women’s Health Resource Center.

I have never read before that men are half as likely to get dry eye - that's quite a lot higher than I would have thought. Wonder where the data is from.

Women who are pregnant, on certain types of birth control, or experiencing menopause have increased rates of Dry Eye. In fact, according to the National Eye Institute, women who are on hormone replacement therapy are also more likely to experience symptoms. Women taking only estrogen are 70 percent more likely to experience Dry Eye, and those taking estrogen and progesterone have a 30 percent increased risk of developing the condition.

That's a nice sum-up - very few sources ever mention birth control as a potential factor or differentiate amongst hormone supplements.

Abstract: Does MG expression help?

This is really quite interesting, though I think it raises many more questions than it answers.

Changes in the Evaporation Rate of Tear Film After Digital Expression of Meibomian Glands in Patients With and Without Dry Eye.
PURPOSE: To evaluate the effect of excess meibum on tear evaporation rate in patients with and without dry eye.

METHODS: Eleven healthy subjects and 16 patients with dry eye were tested. The dry eye group was divided into 2 subgroups: classic keratoconjunctivitis sicca (KCS) with clear and easily expressed meibum and KCS with meibomian gland dysfunction (MGD) with turbid secretions and difficult-to-express meibum. Evaporative measurements were performed at baseline and after digital expression of meibomian glands at 12, 24, 36, and 48 minutes. Two ranges of relative humidity were used, 25% to 35% and 35% to 45%. The data were expressed as microliters per square centimeter per minute.

RESULTS: An increase in the evaporation rate of the tear film was noted for all measurements at both relative humidities in the classic KCS and KCS with MGD groups compared with healthy subjects (P < 0.05). The average evaporation rates at relative humidities of 25% to 35% and 35% to 45% were 0.056 ± 0.016 and 0.040 ± 0.008 for the classic KCS group; 0.055 ± 0.026 and 0.037 ± 0.019 for the KCS with MGD group and 0.033 ± 0.012 and 0.023 ± 0.008 for the healthy group. Also, a decrease in the evaporation rate was observed in the healthy and KCS with MGD groups between baseline and the first measurement after digital expression for both relative humidities (P < 0.05). The classic KCS group did not show any changes after expression.

CONCLUSIONS: Classic KCS and KCS with MGD groups showed an increase in tear evaporation rates compared with the healthy group. Aqueous tear evaporation diminished in the healthy and KCS with MGD groups after expression of meibomian glands. However, this effect was transient and negligible after the second measurement.

Cornea. 2011 Mar 28. [Epub ahead of print]
Arciniega JC, Wojtowicz JC, Mohamed EM, McCulley JP.
From the Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, TX.

Abstract: Beating up on BAK again

Deservedly, of course. This abstract is from a literature review on the subject.

[Ocular toxicity of benzalkonium.]
[Article in French]

In order to meet the requirements of the pharmacopeia, ophthalmic preparations have to be manufactured in conditions that can secure their sterility before use and can prevent the development of micro-organisms after opening of the vial. The addition of an appropriate preservative is a way to meet this requirement. However, in addition to their lack of efficacy in certain conditions, they can be problematic in terms of formulation, stability and interaction with the packagings. Furthermore, their daily and repeated use in chronic pathologies such as glaucoma, dry eye or allergy has revealed their nuisance. Moreover, the recognition of certain parameters such as life quality and therapeutic observance has strengthened the proofs that have already been clinically shown. The review of the experimental and clinical data already published about the toxicity of the preservatives shows that almost every ocular structure is affected to various extents. From the first assumption data to preclinical and clinical proofs, this article highlights the evolution of the understanding process towards the toxic role of preservatives.

Ann Pharm Fr. 2011 Mar;69(2):108-115. Epub 2011 Feb 3.
Chibret H.
Laboratoires THEA, 12, rue Louis-Blériot, 63100 Clermont-Ferrand, France.

Abstract: Pitting 8β-Glycyrrhetic Acid against HMGB1 protein

Well, we might not know or care what all the gobbledegook means right now but one never knows what polysyllabic studies today might turn into a serious dry eye drug contender tomorrow.

18β-Glycyrrhetic Acid Inhibits Immune Activation Triggered by HMGB1, a Pro-inflammatory Protein Found in the Tear Fluid during Conjunctivitis and Blepharitis.

High-mobility group proteins are chromatin-binding factors with key roles in nuclear homeostasis. Evidence indicates that extracellularly released high-mobility group box 1 protein (HMGB1) behaves as a cytokine, promoting inflammation and disease pathogenesis. HMGB1 release occurs during endophtalmitis or uveoretinitis.

Methods: The authors investigated the presence of HMGB1 in tear fluid of patients with different inflammatory disorders of the external eye.

Results: Data demonstrate that HMGB1 content is close to detection limit in tears of control subjects but highly increased (about 15-fold) in patients with conjunctivitis or blepharitis. The authors also report that 18β-glycyrrhetic acid impairs antibody recognition of HMGB1, suggesting direct binding to the protein. Accordingly, 18β-glycyrrhetic acid prevented HMGB1-dependent COX2 expression and cluster formation in primary cultures of human macrophages.

Conclusion: Together, these findings suggest that HMGB1 contributes to inflammatory disorders of the external eye, and 18β-glycyrrhetic acid may scavenge the protein and inhibit its detrimental effects.

Ocul Immunol Inflamm. 2011 Mar 22. [Epub ahead of print]
Cavone L, Muzzi M, Mencucci R, Sparatore B, Pedrazzi M, Moroni F, Chiarugi A.
Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy.

Products: More dry eye supplements

They're popping up like mushrooms these days.

Macular Health announced a dry eye formula with fish, borage seed and flax seed oils and other ingredients.

ZeaVision has developed a dry eye supplement called EyePromise EZTears with fish oil, evening primrose oil and other ingredients.

When I post stuff like this, please bear in mind it's informational only, not a "Rebecca Recommends..." page. If you're shopping for an Omega 3, do your homework, post questions on the bulletin board and be sure to compare EPA/DHA values.

Abstract: Another one on the evils of BAK-preserved glaucoma meds

[Challenge and treatment strategy for ocular surface damage in patients with long term use of antiglaucoma drugs.]
[Article in Chinese]

Long term use of topical anti-glaucoma drugs has been shown to induce chronic conjunctivitis, superficial punctate keratitis (SPK) and dry eye symptom. Under these conditions, a loss of goblet cells in conjunctiva, epithelial squamous metaplasia and apoptosis were morphologically revealed. Benzalkonium Chloride (BKC), a most frequently used preservative in eye drops, has been found to be an important factor causing ocular surface damage. Furthermore, a big challenge for ophthalmologists is that toxic damage of medication to ocular surface tissues is mild, poor specificity, and delayed manifestation in patients, especially when coexisting with other ocular surface diseases. Impairment of ocular surface tissues greatly impacts the life quality of patients and subsequently influences compliance with glaucoma therapy. This paper emphasizes to take measures to prevent ocular surface tissue damage resulted from chronic use of topical anti-glaucoma drugs and further discusses the treatment strategy. Effective and long-lasting action drugs should always be selected for glaucomatous patients in order to decrease the frequency of topical instillation or at a more expensive medication, a fixed combination formula can be considered for glaucoma therapy. An early surgery or laser treatment is also proposed for the patients who require an IOP reduction with an existing ocular surface impairment. Future investigation and development of new medications with long-term efficacy and appropriate BKC are suggested and preservative-free or drugs with new preservative materials recommended.

Zhonghua Yan Ke Za Zhi. 2011 Feb;47(2):101-104.
He XG.
Department of Ophthalmology, The Third Affiliated Hospital, The Third Military Medical University, Chongqing 400042, China. Email:

Abstract: Progress on artificial cornea development

Degradation studies and biological behavior on an artificial cornea material.

Patients suffering from dry eye syndrome, Stevens-Johnson syndrome or have had recurrent transplant rejections are unsuitable to receive a keratoprosthesis. The present work aims at developing a highly biocompatible keratoprosthesis that could be successfully implanted in such patients. Methods and materials:

Methods and materials:
Glass-reinforced hydroxyapatite (GRHA) was used to construct this new artificial cornea. In order to grant the device an adequate porosity, a porogen agent was added in the following percentages, 10, 30 and 50 %. Samples were physicochemically analyzed in terms of density, porosity, roughness, degradation and surface imaging. Biological relevance was assessed by cell culture, MTT assays, and cell imaging.

Samples B (30 %porogen) and C (50 %porogen) were found to be the most porous and also had the roughest topography. Degradation studies showed that under simulated physiological conditions, no mass loss was observed. Conversely, under acidic conditions, a significant mass loss was observed. The biological performance of these samples was satisfactory when cultured with human fibroblasts. The MTT assay revealed that samples B and C had greater propensity to cell invasion and proliferation than the other tested materials. Cell imaging demonstrated that fibroblasts organized around the pore edges before colonizing it.

A material with physical-chemical and biological characteristics close to an ideal artificial cornea has been fabricated. The GRHA cornea containing 30 % porogen is the most promising substitute material due to the biological performance, adequate porosity and low degradation propensity.

Invest Ophthalmol Vis Sci. 2011 Mar 18. [Epub ahead of print]
Santos L, Ferraz MP, Shirosaki Y, Lopes MA, Fernandes MH, Osaka A, Santos JD.
CEMUC, Departamento de Engenharia Metalúrgica e dos Materiais, Faculdade de Engenharia, Universidade do Porto, Portugal.

Abstract: Desiccating stress and mucin deficiency

Entrapment of Conjunctival Goblet Cells by Desiccation-Induced Cornification.

To evaluate the effects of desiccating stress on conjunctival goblet cell density and morphology and expression of cornified envelope precursors by the ocular surface epithelia.

Experimental dry eye (EDE) was created in C57BL/6 mice. Real time PCR evaluated the expression of cornified envelope (CE) precursor proteins (involucrin, small proline-rich [Sprr] protein 1a, 1b, 2a, 2b, 2f, and 2g), the cross-linking transglutaminase 1 enzyme (Tg-1) and Muc5AC mRNA transcripts by the ocular surface epithelia. Laser scanning confocal microscopy evaluated the expression of CE precursor proteins, Tg-1 and Muc5AC in cryosections. Tg-1 activity was measured by a fluorescein cadaverine assay. Muc5AC concentration was measured by ELISA.

Levels of involucrin, Sprr-1a, -1b, -2a, -2b, -2f, and -2g and Tg1-1 mRNA transcripts in ocular surface tissues increased in response to desiccating stress. Expression and activity of Tg in the conjunctiva markedly increased after EDE. Desiccating stress caused progressive loss of mucin-filled goblet cells. The apical portion of remaining conjunctival goblet cells became entrapped by adjacent stratified apical epithelia expressing increased levels of cornified envelope precursors.

Exposure to desiccating stress stimulates ocular surface epithelia to produce of cornified envelope precursors and the tissue transglutaminase enzyme that cross links them. This is accompanied by loss of mucin-filled goblet cells and entrapment of mucin contents in remaining ones by cornifying cells that block egress of mucin contents to the ocular surface. This mechanism may contribute to the conjunctival mucin deficiency that develops in dry eye.

Invest Ophthalmol Vis Sci. 2011 Mar 18. [Epub ahead of print]
Corrales RM, de Paiva CS, Li DQ, Farley WJ, Henriksson JT, Bergmanson JP, Pflugfelder SC.
Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas;

Abstract: Work productivity impact from dry eye

Work productivity loss in patients with dry eye disease: an online survey.

Abstract Objective:
To assess the impact of dry eye disease (DED) on productivity.

Research design and methods:
A cross-sectional, web-based survey was administered to 9034 individuals who are part of the Harris Interactive Online dry eye panel. Patients (≥18 years of age) were included if they were currently employed, a United States resident, had a patient-reported physician-diagnosed dry eye, and scored 13 or higher on the Ocular Surface Disease Index (OSDI). Work productivity and impairment in daily activity was measured using the validated Work Productivity and Activity Impairment (WPAI) Questionnaire. Comparisons were made across disease severity groups: mild, moderate, severe.

Reduced productivity while at work was reported by patients in all three severity groups. Patients with moderate (18%) and severe (35%) disease had significantly greater reductions in productivity than patients with mild (11%) disease, P < 0.05. Impairment in ability to perform daily activities was significantly greater among respondents with severe disease (34%) than respondents with moderate (19%) or mild (12%) disease, P < 0.05.

DED is associated with work productivity loss and impairment of daily activities. These results should be interpreted in the context of limitations related to online survey research.

Curr Med Res Opin. 2011 Mar 21. [Epub ahead of print]
Patel VD, Watanabe JH, Strauss JA, Dubey AT.
Allergan, Inc., Irvine, CA, USA.