Clinical Challenges: Meibomian Gland Dysfunction Underdiagnosed and Undertreated

Meibomian gland dysfunction (MGD) is underdiagnosed and undertreated, with asymptomatic disease far more common than symptomatic disease. As the condition progresses, patients who were initially asymptomatic may develop more advanced disease to the point of requiring treatment.

One of the challenges for clinicians is to identify this slowly progressing disease early, when it is more easily treatable.

An estimated 70% of Americans over age 60 have MGD, and prevalence increases with age, and appears to be higher in men than in women.

A number of factors can influence the physical and functional status of the meibomian glands and lead to loss of function, morphologic changes, atrophy, and gland dropout: the aging process, alterations in sex hormones and the expression of their receptors, nutritional status, reduced blinking, medications, infections, and disease conditions such as seborrheic dermatitis.

Risk factors for MGD also include systemic conditions such as Sjögren's syndrome, Stevens-Johnson syndrome, psoriasis, atopy, polycystic ovary syndrome, and hypertension. In addition, certain ophthalmic factors, including aniridia, chronic blepharitis, contact lens wear, eyelid tattooing, trachoma, and Demodex folliculorum infestation, have been shown to impact meibomian gland function.

The use of antibiotics, isotretinoin for acne, antihistamines, antidepressants, and hormone-replacement therapy may also be associated with MGD.

Definition and Clinical Signs

The International Workshop on Meibomian Gland Dysfunction defines MGD as "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."

MGD can lead to altered tear film composition, ocular and eyelid discomfort, and evaporative dry eye.

The clinical signs of MGD vary, including changes in eyelid morphology, altered secretions, and gland dropout. But not all patients have all clinical features. In fact, these clinical features are often disparate. For example, Black patients are just as likely as white patients to have altered meibum consistency, but Black patients rarely have visible eyelid margin telangiectasias.

Dry eye disease (DED) is an umbrella term that has four components, noted Pedram Hamrah, MD, of Tufts Medical Center in Boston. These include tear deficiency, lipid layer deficiency from MGD, inflammation, and neurosensory abnormalities.

DED symptoms are typically different with MGD. "With MGD, patients wake up fine, but their eyes worsen during the day because the lipid layer is missing, and the symptoms get progressively worse into the afternoon and evening," Hamrah explained.

Clinicians need to look for signs of MGD to diagnose and then treat it at an early stage. "Ignoring the slow progression of MGD makes it more difficult to treat," Hamrah continued. For patients with allergic conjunctivitis, seasonal allergies from pollen may cause a flare-up of the condition.

Asymptomatic disease may lead to symptoms for aging patients, or after 10 to 15 years of everyday computer use. "The lack of blinking while watching a computer screen means the meibomian glands don't squeeze as much, and this exacerbates MGD," Hamrah said. Dry environments also lead to more rapid disease deterioration because of scarification.

Evaluation of MGD

The diagnosis of MGD is straightforward based on clinical examination. It begins by examining the ocular surface and lid margin tear meniscus in association with altered anatomical features, such as terminal duct obstruction, gland dropout, qualitative and quantitative changes in meibum, and pathological events leading to MGD. A detailed assessment is needed to look for associated signs of ocular surface damage or dry eyes.

A step-wise approach for evaluating patients presenting with ocular surface disorder symptoms can be planned based on the initial clinical examination. In general, this entails:

• Administering a validated questionnaire to measure symptoms quantitatively

• Calculating the blink rate and noting the pattern of blinks

• Measuring lower tear meniscus height, tear osmolarity, and tear film break-up time

• Administering Schirmer's test

• Grading conjunctival and corneal staining

• Mass spectrometry to look for the presence of inflammatory cell markers

• Interferometry for lipid layer assessment

If the diagnosis is still not precise, the patient should be assessed for quantification of morphologic lid features, quantification of meibum expressibility and quality, and meibography for quantification of dropout.

Treatment

MGD management starts with physical therapy and then moves on to oral medications, topical medications, and mechanical treatments.

"The first line of therapy is lid hygiene to remove debris on lashes, keratin, or plugs to release obstruction to let the underlying oil flow," said Anat Galor, MD, MSPH, of the University of Miami Health System.

At-home therapy includes a heated mask and gentle eye massage to revive the meibomian glands. Over-the-counter products include medicated pads with different components, such as tea tree oil. If patients are symptomatic, Hamrah suggests artificial tears with lipid, mineral, or flax seed oil.

Second-line therapy escalates to oral or topical antibiotics and in-office treatment. "If the eye is inflamed, I use a short course of topical steroids for 2 to 4 weeks," said Galor. "I may prescribe doxycycline 50 mg once a day for 1 month on, 1 month off, or azithromycin 500 mg 1 week for 8 weeks."

Although both oral azithromycin and doxycycline improve MGD symptoms, a randomized, double-masked, open-label clinical trial found that 5 days of oral azithromycin had a better effect on improving the signs, and resulted in a better overall clinical response and a shorter duration of treatment compared with doxycycline.

Topical azithromycin is a potent antibiotic, used off-label, that provides effective, well-tolerated therapy with immunomodulatory and anti-inflammatory effects that are separate from direct antibacterial actions. Azithromycin ophthalmic solutions penetrate into the ocular surface where it remains at therapeutic levels for a long time.

Hamrah may also use topical erythromycin gel rubbed into the eyelid to decrease inflammation and bacteria at the lid margin, and allow the meibomian glands to open.

Other topicals include compounded testosterone drops or creams, diquafosol, tacrolimus ointment, vitamin D, honey, green tea extracts, and Demodex treatment. Topical cyclosporine A may improve tear film stability as well as subjective ocular discomfort, and can be effective in controlling the lid margin inflammation.

Omega-3 essential fatty acids (EFAs) suppress inflammation, and some small studies suggest that ingesting EFAs may improve meibomian fluidity and secretion.

In-office mechanical treatments may include thermal or light pulsation, and devices such as the LipiFlow Thermal Pulsation System help liquefaction of meibum and prevent tear evaporation.

"If the meibomian glands are partially obstructed, intense pulsed light (IPL) shrinks blood vessels around the glands, reduces the source of inflammation, and stimulates glands to release more oil," said Hamrah.

IPL therapy is a safe and effective adjuvant therapeutic strategy for MGD-related DED. The non-invasive treatment is usually well tolerated, with only rare adverse reactions.

Another in-office device, BlephEx, is a small rotating brush that spins quickly, which Galor said she uses to knock keratin or debris off the lashes with an aggressive scrub.

For patients who have severe scarring and obstruction around the meibomian glands, physical treatments may not be enough. Meibomian gland probing involves opening and dilating blocked ducts by the insertion of small probes. Studies have shown significant improvement in the signs and symptoms of MGD after probing, with immediate symptom relief. Some patients, however, may still need additional probing.

"Once the glands open and flow is reinstated, then I go back to other therapies," said Hamrah.

In general, MGD is a chronic condition that requires regular follow-up. Everyone over age 40 should see an eye doctor once a year and have an ocular surface exam, said Galor.

"We can control MGD and reverse progression, but we can't cure it," Hamrah cautioned. "Symptoms may recur if the patient goes off treatment, and therefore it requires long-term therapy and monitoring."

Patient education about MGD is critical, Hamrah emphasized.

"We can easily manage early cases of MGD," he said. "It's quite important for patients to understand what treatments are needed and that their disease can improve. At-home therapy is like brushing teeth. We can prevent MGD from progressing if we intervene early."

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