MEIBOMIAN GLAND DYSFUNCTION

Signs and Symptoms

Meibomian gland dysfunction (MGD) represents a chronic disorder of the lids, lid margins and preocular tear film. As a rule, the condition is bilateral, although there may be asymmetry in terms of severity. Patients with MGD may report a wide range of symptoms that are characteristically coincident with those of dry eye disease, including burning, dryness, grittiness, itching, foreign body sensation, heaviness of the lids and, in some cases, excessive tearing.1 Fluctuating vision throughout the course of the day may also be among the complaints. Additionally, patients may express cosmetic concern regarding red and swollen lid margins. MGD demonstrates no proclivity toward a specific race or gender and can be seen at any age, although the prevalence does appear to be higher in elderly patients.2

The signs associated with MGD also vary considerably. In some cases, symptoms may precede signs to the point that nothing unusual is encountered on routine biomicroscopic evaluation. This has been dubbed “nonobvious obstructive MGD” by one group of researchers.3 The earliest signs of MGD include foamy or frothy tears, which may be noted along the lower lid margin or at the canthal regions; this is likely due to saponification of tear lipids secondary to bacterial lipases.4 In later stages, clinicians may observe inspissated or capped meibomian glands, as well as thickening, irregularity and hyperemia of the eyelid margins.5 Meibomian gland orifices may demonstrate opacification, periductal fibrosis and posterior displacement toward the mucocutaneous junction.6 Chronically inflamed lids may also display telangiectasis along the margin near the gland orifices and potentially extending to the lash line.

Testing for MGD must include manual expression to evaluate the consistency of the meibum. The clear oil that is expressed with minimal gland manipulation in normal patients becomes thickened and turbid in MGD, often with a buttery or toothpaste-like consistency. Sometimes, excessive pressure is required to liberate meibum from the glands.1 As the disease progresses, obstruction of the glands may lead to structural damage, gland truncation and dropout.7,8 Clinically, this can be observed as a loss of gland density on lid transillumination, infrared meibography, or both.9 Other nonspecific clinical signs of MGD may include diminished tear stability in the form of reduced fluorescein break-up time, punctate corneal and conjunctival epitheliopathy and conjunctival hyperemia.

Pathophysiology

The meibomian glands are modified sebaceous glands, localized within the tarsus of the upper and lower lid; they function to secrete the lipid component of the preocular tear film, commonly referred to as meibum. In normal individuals, there are 25 to 40 glands in the upper eyelid and 20 to 30 in the lower eyelid.3 Current thinking suggests that MGD is primarily an obstructive disorder, rather than an inflammatory or infectious one as was once believed. Clinical and histopathologic studies reveal that terminal duct occlusion due to hyperkeratinization of the ductal epithelium within the glands is the most significant etiologic factor in the pathogenesis of MGD.5,8,10,11 Obstruction leads to dilatation of the ducts as well as intraglandular cystic degeneration and loss of secretory meibocytes, resulting in downregulation of glandular function and progressive damage to the gland structure.5 The obstructive process is believed to be influenced by both endogenous and exogenous factors, including age, diet, hormonal alterations and chronic use of topical medication.8 Cumulative contact lens wear has also been associated with a decrease in the number of functional meibomian glands.12

Also contributory to the pathology of MGD, meibum secreted by these obstructed glands has been shown to be more saturated and contain less branched chain hydrocarbons and more protein.13 This change results in more ordered, more viscous lipid secretions, which diminishes the flow and impedes the delivery of meibum to the lid margin. Stagnated meibum means that less lipid is available to form the tear film, resulting in diminished tear stability and increased tear evaporation.14

As a consequence of MGD, hyperosmolarity of the tear film may drive inflammation of the ocular surface, as well as increased growth of bacterial lid flora such as Propionibacterium acnes and Staphylococcus epidermidis, which thrive in this environment.15 These bacteria secrete lipases, which act directly on the meibum and initiate conversion of the lipids into free fatty acids and soaps. These unwanted elements in turn cause ocular surface irritation and further disrupt the tear film.14 Recalcitrant forms of MGD may be associated with rosacea, a generalized dermatologic condition affecting the sebaceous glands of the face, particularly the nose, cheeks, forehead and periorbital regions.

Management

There exists a broad range of treatment options for MGD, depending upon the severity of the disease and the disposition of the patient. The Report of the International Workshop on Meibomian Gland Dysfunction, published in 2011, delineated a staged treatment algorithm for MGD consistent with disease severity.16 Among the recommendations were: patient education; eyelid hygiene with lid warming and gland expression; liberal use of ocular lubricants (particularly those with a lipid base) and lubricant ointments at bedtime; increased intake of omega-3 fatty acids; topical azithromycin; oral tetracycline derivatives; and anti-inflammatory therapies for dry eye in the most severe cases.

Eyelid warming—also known as lid hyperthermia—with concurrent or subsequent massage to help express the meibomian glands has long been considered the mainstay of MGD management. The direct application of heat (approximately 105°F to 110°F) to the lid margins helps to improve circulation in the lids and lower the viscosity of meibomian secretions, allowing them to flow more freely.17,18 While numerous modalities can be employed as warm compresses, including hot soaked towels, hard-cooked eggs, rice socks and commercially available hot packs, it is important to use an item that can retain and generate consistent temperatures for at least five minutes.19 With the addition of gentle pressure along the lid margins, sequestered meibum can be released from the glands to a significant degree. One study reported increases in lipid layer thickness of more than 80% after just five minutes of such treatment.20 However, patients employing this form of therapy must be warned against vigorous rubbing of the eyelids, as that activity, on a chronic basis, holds the potential for corneal warpage.21-23 Newer modalities such as intense pulsed light (IPL) therapy, LipiFlow vectored thermal pulse technology (TearScience) and MiBo ThermoFlo meibomian duct therapy (Pain Point Medical Systems) provide an option for in-office lid hyperthermia with concurrent or subsequent gland expression. Numerous studies have demonstrated the efficacy of these treatments for MGD.24-28

Ophthalmic lubricants may be quite helpful in MGD, particularly those that contain a lipid component; these products are typically labeled as emulsions or emollients. A recent open-label study of one such product in patients with MGD demonstrated not only improvement in subjective symptoms, corneal staining and tear break-up time, but also a mild but statistically significant improvement in meibomian gland expression scores.29

Diets or nutritional supplements rich in omega-3 essential fatty acids may also benefit the MGD patient by one or more proposed mechanisms. One hypothesis suggests that, since the metabolic breakdown of omega-3 fatty acids results in liberation of tear-specific anti-inflammatory prostaglandins, increasing omega-3s in the diet leads to diminished ocular surface and eyelid inflammation.30,31 Another school of thought maintains that supplementation with omega-3 fatty acids may positively impact overall fat composition in the body, thereby improving the lipid properties of the meibum.32

Unfortunately, simply recommending nutritional modifications or supplements is not enough. Patients need to be directed toward appropriate products and dosing. The most readily bioavailable source of omega-3 fatty acids comes from cold-water fish such as mackerel, wild salmon, sardines and anchovies. Processed sources of fish oil should be in the triglyceride form, rather than the ethyl ester form, to maximize bioavailability.33 A daily total of 2,000mg or more is typically required to instigate a positive effect on meibomian gland health; however, patients just starting on omega-3 supplements should be briefed on their side effects, notably increased urination and gastric distress. Patients may need to slowly build up tolerance to the product, beginning at 1,000mg/day and increasing slowly over two to three weeks. Patients taking systemic anticoagulant or antiplatelet therapy—such as aspirin, warfarin, Plavix (clopidogrel, Bristol-Myers Squibb) or Ticlid (ticlopidine, Roche Laboratories)—should check with their primary care doctor before starting omega-3 supplements, since there exists a potential dose-related risk for increased bleeding time.34,35

AzaSite (topical azithromycin, Akorn) has also demonstrated efficacy in this arena. Though the mechanism of action is poorly understood, a series of published studies involving AzaSite has shown distinct improvement in both signs and symptoms of MGD.36-38 The typical regimen is one drop twice daily for two days, then one drop at bedtime for an additional four weeks. Patients are advised to instill the drop into the lower cul-de-sac, close their eyes gently, and then spread the residual medication along the lid margins with a clean finger. While this medication is not specifically FDA-approved for MGD, it has been shown to be safe and effective in its management.36-38

Oral tetracycline derivatives such as doxycycline or minocycline have long been used as a treatment option for chronic or recalcitrant MGD. It is believed that these drugs hinder the production of bacterial lipases, which serve to alter the consistency of the meibomian lipids.39 Additionally, tetracyclines are recognized to be potent anti-inflammatory agents, inhibiting the expression of matrix metalloproteinases and other cytokines.40,41 A regimen of oral doxycycline 100mg BID for four weeks, then QD for another four to eight weeks, has been shown to be highly effective.42 Therapeutic effects may be seen with as little as 40mg of doxycycline hyclate daily, though at this decreased dosage there is typically a delayed response, often taking up to six weeks for patients to have symptomatic improvement.43

Anti-inflammatory therapies are reserved for the most severe forms of MGD or those with concurrent ocular surface disorders such as aqueous deficient dry eye. Many clinicians prefer to use a combination agent with a concurrent steroid and antibiotic. Unfortunately, the long-term effects of corticosteroids must always be weighed against the benefit of any chronic disease. Most experts recommend corticosteroids for short-term use only—usually two weeks or less—in an effort to jump start therapy for moderate-to-severe disease.44 Restasis (topical cyclosporin A, Allergan) may be substituted for long-term therapy in these cases. However, Restasis is nonspecific for MGD and may not provide the relief that patients seek quite as effectively as some of the therapies discussed.44

One of the recent interventions for MGD involves debridement scaling of the posterior lid margin. One report described a procedure in which researchers passed a golf-club spud firmly along the lower lid at the region overlying the meibomian gland orifices. After following these subjects for four weeks, the authors noted significantly reduced symptom scores and an increased number of glands expressing meibum, as compared to subjects in the control group.45 In clinical practice, the BlephEx device (BlephEx) appears to provide a much more thorough and tolerable means to debride the obstructed meibomian glands, removing additional, toxin-laden debris from the lid margins. Another recent study demonstrated the efficacy of this device in treating patients with MGD. After a single BlephEx procedure, subjects exhibited significantly diminished MGD severity, increased tear break-up time and reduction of clinical symptoms by over 50% at four weeks post-treatment.46

Clinical Pearls

The epithelial lining of the meibomian ducts is naturally devoid of pigment. Subsequently, patients with darker skin may appear to have inspissated glands upon routine inspection, while fair-skinned patients may appear to have unobstructed glands. For this reason, it is crucial to perform diagnostic gland expression on all patients to ascertain what lies beneath the surface.

Interferometric imaging of the ocular surface can be helpful in assessing the quality of the lipid tear layer, as a means to reveal evaporative dry eye and MGD. Two such devices that can perform this testing are the Keratograph 5M (Oculus) and the LipiView II (TearScience). These instruments are also capable of performing infrared meibography, in addition to other tests for ocular surface disease.

The use of lid scrubs with surfactant cleaners is often employed in the treatment of anterior blepharitis, but may be of limited value in MGD. Because this disorder involves a lipid deficiency, and since surfactant cleansers function to remove oil, aggressive cleansing of the lid margin with baby shampoo or commercial detergent cleansers may be self-defeating. Rather, we recommend a nonsurfactant cleanser such as Avenova (NovaBay Pharmaceuticals), which addresses excessive lid margin bacteria and inflammatory mediators by incorporating a stable hypochlorous solution.

Patient education is crucial to success in the management of MGD. A discussion of the progressive nature of this disorder as well as the need to alleviate meibomian gland obstruction helps patients to better understand the implemented therapeutic measures.

Elements that additionally impact MGD include diet, the effect of work/home environments on tear evaporation and the possible drying effect of certain systemic medications; these should be communicated as well.

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46. Connor CG, Choat C, Narayanan S, et al. Clinical effectiveness of lid debridement with BlephEx treatment. Poster #4440, presented at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO). Denver, CO; May 06, 2015.