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Back in my early clinical training at Berkeley, I remember a patient, a college-age Asian male who was in clinic for a contact lens fitting. Sounds like a regular day in clinic, right? On eyelid eversion, his upper left lid margin showed a single dome-shaped capped gland. Readers, you can picture this because you have seen it many-a-time. The “cap” looks slightly yellow, smooth, and slightly waxy. More importantly, you have the urge to pull out the wood end of a cotton swab and try to “pop” it off. While there is plenty I do not remember about my clinical experiences early on, for some reason I remember this event. I wrote: “LUL capped gland” in the record, and that was it. I didn’t mention it to my attending, we fit the patient in contact lenses, and everyone was happy. How many times have we all experienced this exact scenario?

Fast forward to ARVO 2010, when I am having a delightful discussion with Professor Tony Bron, MD, of Oxford, England. We were discussing this very topic—and when I described this patient he said: “I always treat a patient with a single capped gland. A capped gland indicates that every gland in that eye has the potential to be abnormal, whether in quality or quantity of meibomian gland secretions.” There was a moment of silence. And then a few more. Profound.

As we discuss expression and evaluation of the meibomian glands with today’s technology, such as meibography and a variety of gland “expressors,” it is important to remember that our eyes are important “tools” as well. Channel the esteemed Dr. Bron and ponder this question—If you see a capped gland, isn’t the diagnosis of MGD already made? Observational skills can be just as informative as technology, and meibography and gland expression along with observation should be used to guide a step-wise management plan and monitor change over time with treatment.

Anyone wonder if my patient is comfortable in his contact lenses today? I sure do. We have come a long way in our understanding of ocular surface disease, but when faced with the single capped gland that is screaming out MGD, let’s hope we all take notice.



Kelly K. Nichols, OD, MPH, PhD
Editor

July 24, 2014
Editor's Commentary
News
Nicox Focuses U.S. Operations on National Launches of Sjö and RetnaGene

B+L Recall of Muro 128 5% Eye Ointment

Clinician's Corner: Meibomian Gland Disease (MGD) – Why Is Meibography Important?
Research Update: Commentary on Abstract of the Week
Abstract
Dry Eye 101: Nuts and Bolts: with video feature


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NEWS

Nicox Focuses U.S. Operations on National Launches of Sjö and RetnaGene
Nicox S.A. announced that Nicox’s subsidiary, Nicox Inc, will focus its U.S. sales force on supporting the national roll-out of Sjö, an advanced diagnostic panel for the early detection of Sjögren’s syndrome in patients with dry eye, and on promoting the RetnaGene portfolio including RetnaGene AMD and RetnaGene LR, specialized genetic tests which assess an individual’s risk for advanced age-related macular degeneration (AMD). Nicox and Rapid Pathogen Screening (RPS) have therefore agreed to restructure the terms of their partnership in North America. Effective August 1st, 2014, RPS will resume responsibility for marketing AdenoPlus, a point-of-care diagnostic test that aids in the differential diagnosis of acute conjunctivitis, to eye care professionals in North America, as well as two other diagnostic products currently in development. RPS will pay a royalty on sales to Nicox. Nicox will continue to have rights to commercialize AdenoPlus and the previously licensed development products in all markets outside of North America.

Nicox recently initiated the national expansion of Sjö for the early detection of Sjögren’s syndrome in patients with dry eye. Sjö was launched in select U.S. markets in November 2013. Utilizing the expanded sales force put in place in June 2014 Nicox is now marketing Sjö to eyecare professionals throughout the U.S. under an exclusive North American agreement signed with Immco Diagnostics Inc. in June 2013. Eyecare practitioners are in a unique position to identify Sjögren’s syndrome as dry eye is a significant and early symptom of the condition.

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B+L Recall of Muro 128 5% Eye Ointment
Some recent news stories reported on an ongoing recall of close to 850,000 tubes of Bausch + Lomb’s Muro 128 5% Ointment (Sodium Chloride Hypertonicity Ophthalmic Ointment, 5%) related to crystallization with crystal precipitate formation and an increase in the number of complaints associated with a gritty, sand-like feeling in the eye. The OTC product is intended for temporary nighttime relief for individuals suffering from corneal edema.

The Wall Street Journal reports1 that B+L voluntarily initiated the recall earlier this year. The same article states that B+L said affected products may have been exposed to freezing temperatures after leaving company-owned facilities and that freezing temperatures can cause the crystal formations in the salt-based product. Boxes containing the tubes carry a “do not freeze” label.

In a recall notice sent to retailers and distributors on May 30, 2014,2 the company stated it was recalling the product in the interest of public safety due to the increase in the number of complaints related to crystal precipitate formation.

The FDA classified this as a Class II recall:3 a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote. Further details on lot numbers can be found in the Enforcement Report posted on the FDA website.3

1. http://online.wsj.com/articles/bausch-lomb-recalls-about-850-000-tubes-of-eye-ointment-1404418011. Accessed July 10, 2014.
2. https://www.majorpharmaceuticals.com/pdf/recalls/Muro-128-Ointment.pdf. Accessed July 10, 2014.
3. http://www.accessdata.fda.gov/scripts/enforcement/enforce_rpt-Product-Tabs.cfm?action=select&recall_number=D-1410-2014&w=07022014&lang=eng. Accessed July 10, 2014.

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CLINICIAN'S CORNER:
MILD-TO-MODERATE DRY EYE

By Amber Gaume Giannoni, OD, FAAO

Meibomian Gland Disease (MGD) – Why Is Meibography Important?

If you’re managing dry eye disease in your practice, having the ability to assess the structure and integrity of the meibomian glands is a very important step toward developing a successful treatment plan for your patient. For example, although heat therapy and gland expression are often successful therapies for MGD, the patient is unlikely to appreciate a substantial improvement in symptoms if they have advanced atrophic disease: if the glands are gone, they’re gone. Being unaware of atrophic disease can prove to be very frustrating as symptoms will persist even with treatment, and both patient and practitioner might begin to question the other’s commitment and ability.

Another important aspect of successful patient care is setting appropriate and realistic expectations. This is challenging if you don’t have a firm grasp on the disease state from the beginning. In the example above, if you know from the onset that your patient has extreme meibomian gland atrophy, you may still choose to put them on heat therapy to help preserve the function of the remaining glands, but you would also be able to explain why additional treatment is required to fully address their symptoms (i.e. oil-based lubricants, protective eye wear, etc.).

Directly viewing the meibomian glands is achievable in several ways. One inexpensive method is to evert the eyelid over a transilluminator head and view the glands from the palpebral side using your slit lamp oculars (to increase magnification). Admittedly, this takes a bit of practice, but can be done well. If photo documentation is desired, commercial infrared meibography is available which we’ve found greatly enhances patient understanding, in-turn improving overall compliance. Oculus Inc. offers enhanced infrared meibography on their Keratograph 5M as part of their Dry Eye Suite. Interpreting meibography images from the K5M are described in further detail in Dr. Jillian Meadows’ column this week. Lastly, there are other systems available that basically couple your slit lamp with a long-wavelength video camera.1

Regardless of the method you settle on, if you treat dry eye in your practice, direct observation of the meibomian glands (as well as their contents) is essential to the diagnostic process, which ultimately translates to improved patient care.

1. Arita R, Itoh K, Inoue K, Amano S. Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmology. 2008 May;115(5):911-5. doi: 10.1016/j.ophtha.2007.06.031.

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RESEARCH UPDATE:
COMMENTARY ON ABSTRACT OF THE WEEK
Sruthi Srinivasan, PhD, BS Optom, FAAO

There are structural and functional differences between the meibomian glands of the upper and lower eyelids with a higher number and larger size of glands in the upper lid compared to the lower lid.1 Expression of meibum is facilitated by the squeezing of the glands by the contracting muscle fibers of the orbicularis oculi during a blink.1 Expression of meibum from the meibomian glands aids in the prevention of orifice obstruction. Taking into consideration the larger degree of movement of the upper lid during a blink, Eom et al. hypothesized that there would be differences in the meibum quality and meibomian gland loss between the upper and lower eyelids.

In this study by Eom et al, this hypothesis was tested by investigating meibum quality and meibomian gland loss in the upper and lower eyelids of patients with obstructive meibomian gland dysfunction.2 Twenty-six participants, mean age of 58.9 ± 9.9 years (range, 37-74 years) with obstructive MGD participated in this study. There were six males and 20 females. Tear break up time (TBUT) using sodium fluorescein, corneal staining using fluorescein, meibum quality, and meibomian gland loss using a non-contact meibography were evaluated. Results of the study showed that meibum quality was significantly reduced in the lower lid compared to the upper lid. Meibomian gland loss was also significantly higher in the lower lid compared to the upper lid. In both the upper and lower eyelids, meibomian gland loss correlated with expressed meibum grade. TBUT and corneal staining were significantly correlated with only meibum quality, and not with meibomian gland loss.

Limitations of the study as mentioned by the authors include the small sample size. This study demonstrated differences in the degree of meibomian gland loss and meibum quality between upper and lower eyelids and postulated that this is due to the structural and functional differences between the glands. This study raises many important clinical questions—can we just look at the lower lid and assume it will be worse in MG drop out and secretion quality? Does the upper lid “adjust” and provide more meibum when the lower lid is at a deficiency? And most important, how does this correlate with symptoms? Continued studies of this type are needed to aid our understanding of this prevalent condition.

1. Knop E, Knop N, Millar T, Obata H, Sullivan DA. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci. Mar 2011;52(4):1938-1978.
2. Eom Y, Choi KE, Kang SY, Lee HK, Kim HM, Song JS. Comparison of meibomian gland loss and expressed meibum grade between the upper and lower eyelids in patients with obstructive meibomian gland dysfunction. Cornea. May 2014;33(5):448-452.


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ABSTRACT

Comparison of Meibomian Gland Loss and Expressed Meibum Grade Between the Upper and Lower Eyelids in Patients with Obstructive Meibomian Gland Dysfunction

Eom Y, Choi KE, Kang SY, Lee HK, Kim HM, Song JS. Cornea. 2014 May;33(5):448-52.

PURPOSE: The aim of this study was to compare meibomian gland loss (MGL) and expressed meibum grade between upper and lower eyelids in patients with obstructive meibomian gland dysfunction (MGD) and to evaluate the correlation between these 2 parameters and other clinical measurements.

METHODS: Twenty-six eyes of 26 patients with obstructive MGD were enrolled. Upper and lower MGLs were evaluated using noncontact meibography. Expressed meibum quality was assessed in 8 glands of the central third area of the upper and lower eyelids on a scale of 0 to 3 for each gland (total score range, 0-24). Tear film stability was evaluated based on tear break-up time (TBUT), and corneal staining was graded according to the National Eye Institute scale (range, 0-15).

RESULTS: The mean MGL in the lower eyelids (24.1% ± 10.8%) was significantly greater than that of the upper eyelids (11.2% ± 5.2%) (P < 0.001). The mean expressed meibum grade in the lower eyelids (16.5 ± 5.1) was also significantly larger than that of the upper eyelids (11.2 ± 5.2) (P < 0.001). MGL was significantly correlated with expressed meibum grade in both eyelids (r = 0.451, P = 0.021 in the upper eyelids; r = 0.626, P = 0.001 in the lower eyelids). The meibum grades of both the upper and lower eyelids were negatively correlated with TBUT and positively correlated with corneal staining score. However, the MGL in both the eyelids was not correlated with TBUT or with corneal staining score.

CONCLUSIONS: In patients with obstructive MGD, MGL and meibum grade in the lower eyelids were significantly greater than those of the upper eyelids. Although MGL and meibum quality showed a positive correlation with each other, TBUT and corneal staining score were significantly correlated with only meibum grade, and not with MGL.


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DRY EYE 101: NUTS AND BOLTS
By Jillian Meadows, OD, MS, FAAO

Question: What exactly is meibography, how do I do it, and what do the images mean?

Answer: Meibography, a method to observe and photodocument meibomian gland morphology, is becoming an integral component of the comprehensive ocular surface evaluation. Before the Oculus Keratograph, clinicians would apply a transilluminator to the skin side of the everted eyelid to retroilluminate the glands. Though these tools are readily available in clinic, the visibility of the glands was rather poor. The Keratograph uses infrared radiation of 890 nm and displays a high-contrast image for better visibility. Check out our supplemental video on how to acquire meibography images with the Keratograph 5M!


Meibography Imaging Video

Several grading scales have been developed to assess the extent of meibomian gland dropout. While the precise details of each scale may have less impact on your clinical practice, you should keep a few things in consideration when grading meibography images. First, assess the percentage of glands, as compared to the entire observed area, that are truncated. Second, determine the average extent of truncation for the affected glands. For example, Figure 1B below depicts a 60-year-old female with approximately 80% glandular involvement and 30-40% truncation on average (upper lid). Third, make note of atypical patterns, particularly ductal tortuosity. Although tortuosity has been described in patients with meibomian gland dysfunction, it is currently unknown whether it truly represents a pathological process or a benign anomaly in glandular development.

Meibography images are great tools for patient education and disease documentation. But how great is it at tracking response to treatment? This is an ongoing area of research, so I leave you with a few questions to ponder. Do you think meibomian gland dropout is permanent or reversible? Is there a “critical period” during which we can recover, with appropriate intervention, the structure and function of atrophic glands? Similarly, do you hopelessly give up treatment in a patient with extensive dropout, or do you become more aggressive?


Figure 1: (A) A 29-year-old female with essentially normal meibomian gland (MG) morphology, (B) a 60-year-old female with symptomatic, lipid-deficient dry eye and moderate shortening of the superior MGs, (C) a 28-year-old female with no symptoms or clinical signs of dry eye, mild shortening of the superior MGs, and mild ductal tortuosity, and (D) a 38-year-old female with symptomatic, lipid-deficient dry eye, mild ductal tortuosity, and mild to moderate shortening primarily of the inferior MGs.


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