Clearer understanding of precursors of meibomian gland dysfunction warranted

Nonobvious obstructive meibomian gland dysfunction is an area of growing importance.

Steven L. Maskin

There has been increasing focus on the role of meibomian gland dysfunction in ocular surface health and a recent paradigm shift in how to best diagnose, manage and treat it.

Furthermore, the current understanding of meibomian gland dysfunction (MGD) is expanding to now include a newer term for the earlier stage — nonobvious obstructive MGD, or NOMGD, which many experts say may be the most common form of obstructive MGD.

“The greatest untapped area to improve ocular surface disease is the proper diagnosis and treatment of MGD,” Steven L. Maskin, MD, FACS, an ophthalmologist at the Dry Eye and Cornea Treatment Center in Tampa, Fla., said.

NOMGD is the precursor to obvious obstructive MGD. Whereas the prevalence of NOMGD seems to be high, it is still significantly underdiagnosed. Variability in the clinical presentation of patients’ signs and symptoms coupled with the lack of consensus on exact diagnostic criteria make it difficult to diagnose.

“We need a better way to diagnose NOMGD. While the available diagnostic tools are helpful, there is no single test for it, and we need better tools to tell us what treatments are more effective and why,” Edward J. Holland, MD, OSN Cornea/External Disease Board Member, said.

First step: diagnosis

When a patient presents with possible ocular surface disease, Dr. Maskin said, clinicians should break down the complexity of the signs and symptoms into components, then prioritize them for targeted therapy.

Frequent initiators of ocular surface disease include MGD, aqueous tear deficiency, blepharitis, blepharoconjunctivitis, conjunctivochalasis, allergy and environmental exposures. Rosacea and floppy lid should also be identified for possible treatment.

It is important for the clinician to first differentiate which ocular surface disease needs to be treated. “They need to know the signs and symptoms for each, because the treatments are very different and sometimes require a combined therapeutic approach,” Dr. Holland said. “Importantly, we should not assume that there is no disease without inflammation, redness or discharge.”

MGD may present not only without inflammation, but also without any other obvious clinical signs. It is important to note that NOMGD sometimes results in significant symptoms, but without signs, Dr. Holland said. Patients often have early symptoms and complain of an aching eye or discomfort with wearing contacts, for example.

The current belief is that a patient with NOMGD with no detectable inflammation and no meibum upon expression has an underlying obstruction, most likely distally, according to Dr. Maskin. A tender lid suggests elevated intraductal pressure and intact although possibly diminished meibum production, which could indicate acinar demise.

Ultimately, Dr. Holland said the key to diagnosing NOGMD and any ocular surface disease is to simply listen to the patient.

“Diagnosing our patients properly will provide clinicians with the opportunity to target treatments appropriately, which will ultimately impact the patient’s ability to achieve good visual acuity and overall eye health,” he said.

Traditional treatments

Treatment for NOGMD is the same as that for MGD but begins at an earlier stage. The currently available therapies aim to relieve orifice and intraductal obstructions to enable meibum flow.

According to a review published in Cornea by Dr. Holland and colleagues: “Treatment of NOGMD is designed to restore the normal flow of meibomian gland secretions, thereby increasing the likelihood of a healthy lipid layer and consequently enhancing tear film stability.”

Once a case is diagnosed, relief of the obstruction by liquefaction and/or physical expression is often beneficial. The one caveat when treating NOMGD is that therapeutic expression without establishing the status of intraductal obstruction can work against the patient to increase inflammation and result in acinar damage, Dr. Maskin said.

Warm compresses coupled with lid hygiene, another treatment option, help keep the lid margin clean, liquefy solidified meibomian gland contents and promote a healthy noninflamed orifice and distal gland. While this option is safe, cost-effective and convenient, Dr. Holland noted a major compliance issue.

Heat therapy and eyelid scrubs relieve blockage, and medication to mitigate infection and inflammation is warranted, according to Dr. Holland.

Anti-inflammatory steroids and oral antibiotics are additional treatment options. Tetracyclines including doxycycline, tetracycline and minocycline reduce inflammation and improve the secretory lipid profile.

Additionally, Dr. Holland suggested that because patients with MGD have an altered lipid composition, introducing nutritional supplements such as omega-3 and omega-6 essential fatty acid supplements appears to improve the lipid profile of the meibomian gland.

To alleviate symptoms and maintain the health of the ocular surface, tear substitutes are also suggested. The most common ones incorporate aqueous and mucin analogues.

“The benefits of the current treatments are to prevent infection, minimize inflammation and improve the lipid profile; however, none of these treatments can establish or confirm the patency of the intraductal outflow path,” Dr. Maskin said.

A look ahead

“The most exciting area of new developments is intraductal meibomian gland probing, where for the first time we can physically enter the gland and identify obstruction located proximally or distally,” Dr. Maskin said referencing a study published in Cornea.

Studies to date have shown therapeutic benefit, with an 80% reduction in symptoms at 1-year follow-up, and long-term safety of intraductal probing.

“This technology, which has been available for 1 year from Rhein Medical, holds great promise for diagnostic and therapeutic intervention for MGD,” Dr. Maskin said.

Other new therapeutics on the horizon include the LipiFlow thermal pulsation device (Tear Science), which incorporates physical expression to provide a better way to deliver heat to the lids. LipiFlow is being used in Europe and is currently undergoing review for approval by the U.S. Food and Drug Administration.

Dr. Maskin believes AzaSite (azithromycin ophthalmic solution 1%, Inspire Pharmaceuticals) may also have a future role in maintaining the improvement in meibomian gland functioning after intraductal probing.

According to Dr. Holland, “Due to the unique properties of this medication, such as the anti-inflammatory, antimicrobial, improved quality of the meibomian gland secretions and excellent tissue penetration, AzaSite has become first-line therapy for my patients with MGD.”

Additional studies are under way to investigate Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergen) for MGD treatment.

Researchers are evaluating intense pulse light as a possible treatment for MGD in cases of rosacea. Topical androgen hormones are also being evaluated.

To improve the treatment of ocular surface disease overall, better understanding of the glandular and intraductal pathological changes in NOMGD and MGD and how they correlate with findings during meibomian gland probing is needed, Dr. Maskin said.

“I believe great progress is on the horizon,” he said. “MGD is the entity with the greatest potential for impact on the health of the ocular surface.” – by Tara Grassia

References:

• Akpek EK, Vittitow J, Verhoeven RS, et al. Ocular surface distribution and pharmacokinetics of a novel ophthalmic 1% azithromycin formulation. J Ocul Pharmacol Ther. 2009;25(5):433-439.
• Blackie CA, Korb DR, Knop E, et al. Nonobvious obstructive meibomian gland dysfunction. Cornea. 2010;29(12):1333-1345.
• Foulks GN, Borchman D, Yappert M, et al. Topical azithromycin therapy for meibomian gland dysfunction: clinical response and lipid alterations. Cornea. 2010;29(7):781-788.
• Haque RM, Torkildsen GL, Brubaker K, et al. Multicenter open-label study evaluating the efficacy of azithromycin ophthalmic solution 1% on the signs and symptoms of subjects with blepharitis. Cornea. 2010;29(8):871-877.
• John T, Shah AA. Use of azithromycin ophthalmic solution in the treatment of chronic mixed anterior blepharitis. Ann Ophthalmol (Skokie). 2008;40(2):68-74.
• Luchs J. Efficacy of topical azithromycin ophthalmic solution 1% in the treatment of posterior blepharitis. Adv Ther. 2008;25(9):858-870.
• Maskin SL. Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland dysfunction. Cornea. 2010;29(10):1145-1152.

• Edward J. Holland, MD, can be reached at the Cincinnati Eye Institute, 525 South Loop Road, Edgewood, KY 41017; 859-331-9000; fax: 859-331-9040; e-mail: eholland@holprovision.com.
• Steven L. Maskin, MD, can be reached at the Dry Eye and Cornea Treatment Center, 3001 W. Swann Ave., Tampa, FL 33609; 813-875-0000; fax: 813-877-7093; e-mail: drmaskin@drmaskin.com.
• Disclosures: Dr. Maskin has a direct financial interest in Maskin meibomian gland intraductal probes and tubes. He also has a pending patent on the use of jojoba for the treatment of meibomian gland dysfunction or obstruction. Dr. Holland is a consultant for Alcon, Allergan and Inspire Pharmaceuticals.