Meibomian Gland Disease: Treatment

Published on 08/03/2015 by admin

Filed under Opthalmology

Last modified 22/04/2025

Print this page

This article have been viewed 8861 times

Meibomian Gland Disease

Treatment

Gary N. Foulks

Introduction

Meibomian gland disease is one of the most commonly encountered clinical problems and can occur as focal or diffuse involvement of the meibomian glands. Meibomian glands are anatomically located in the tarsal plate of both upper and lower eyelids, as holocrine sebaceous glands that open directly on the eyelid margin and discharge their entire contents onto the lid margin. A full description of the anatomy and physiology of the glands is provided in the Report of the Meibomian Gland Workshop published in 2011.¹ The meibomian gland is a type of sebaceous gland and it is susceptible to disease entities that affect all sebaceous glands, such as seborrhea and rosacea.¹ Since obstruction of the gland orifice and alteration of the meibomian secretion are the predominant pathophysiological causes of disease, management of the clinical problem centers around relief of obstruction and modification of the abnormal secretion, as well as control of inflammation when it occurs as part of the disease process.

Classification of Meibomian Gland Disease

The etiology of meibomian gland disease can be congenital or acquired. A classification system proposed by the International Workshop on Meibomian Gland Dysfunction is depicted in Figure 10.1.² Congenital absence of the meibomian gland occurs and is particularly severe in association with anhidrotic ectodermal dysplasia.³

Figure 10.1 Classification of meibomian gland disease. (Reproduced with permission from Investigative Ophthalmology and Vision Science: Nelson JD, Shimazaki J, Benitez-del-Castillo JM, et al. The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci 2011;52:1930–7.)

Acquired disease occurs as both focal (internal hordeolum or chalazion) or diffuse (meibomian gland dysfunction: MGD) involvement. Although obstruction of the glandular orifice is the likely first event, the clinical appearance is very different, as the internal hordeolum (Fig. 10.2) is the result of an acute bacterial infectious inflammation, while chalazion (Fig. 10.3) is the result of a chronic localized lipogranulomatous inflammation, and meibomian gland dysfunction (MGD) (Figs 10.4 and 10.5) is primarily obstructive with variable inflammatory reaction and typically no active infectious component, although lid margin flora may influence metabolism of the meibum secretion.⁴ Thus, the management of the various clinical manifestations of meibomian gland disease differs in both the pathophysiological target and recommended therapy.

Figure 10.2 Internal hordeolum. Note the acute focal swelling and erythema of the lower eyelid with obstruction of meibomian gland orifice behind lash line.

Figure 10.3 (A) Chalazion: external view. Note the focal swelling in the upper eyelid without significant erythema. (Note also the external hordeolum with acute inflammation in the lower eyelid). (B) Chalazion inner palepebral view.

Figure 10.4 (A) MGD with epithelial obstruction of meibomian gland orifice. (B) MGD with meibomian gland secretion turbidity. (Reproduced with permission of Elsevier. From Foulks GN, Bron AJ. Meibomian Gland Dysfunction. A Clinical Scheme for Description, Diagnosis, Classification, and Grading. The Ocular Surface 2003;1:107–26.) (C) MGD with meibomian gland secretion that is turbid with clumps. (D) MGD with meibomian gland secretion that is paste consistency.

Figure 10.5 (A) Chronic MGD change of telangiectasia of eyelid margin. (B) Chronic MGD with cicatricial obstruction of meibomian gland orifice. (Reproduced with permission of Elsevier. From Foulks GN, Bron AJ. Meibomian Gland Dysfunction. A Clinical Scheme for Description, Diagnosis, Classification, and Grading. The Ocular Surface 2003;1:107–26.) (C) Chronic MGD with posterior traction of meibomian gland orifice due to cicatricial change. (Reproduced with permission of Elsevier. From Foulks GN, Bron AJ. Meibomian Gland Dysfunction. A Clinical Scheme for Description, Diagnosis, Classification and Grading. The Ocular Surface 2003;1:107–26.)

Pathophysiological Targets and Goals of Therapy

Since internal hordeolum is acute suppurative inflammation of the meibomian gland, antibiotic therapy of the infectious component and anti-inflammatory therapy to control the acute inflammation are both appropriate treatments. Relief of obstruction of the gland is also important. The infecting organism is most often Staphylococcus but other bacteria can be present.⁵ No good comparative clinical trials have been published to compare effectiveness of treatment options for internal hordeolum,⁶ but the use of topical antibiotic drops or ointments includes topical erythromycin, bacitracin, tobramycin, or fluoroquinolones. In adults with severe or recurrent disease, oral doxycycline can be prescribed as systemic therapy. Application of warm compresses periodically during the day helps to reduce inflammation and encourages the infection to localize to a point which may spontaneously erupt to relieve the obstruction. Occasionally, surgical lancing of the pointing hordeolum speeds resolution. Anti-inflammatory therapy with topical corticosteroid can be helpful when inflammation is severe.

Since chalazion is a chronic focal reaction of the tissue to altered lipid components of meibum occurring in an obstructed gland, the primary therapy is first anti-inflammatory. Warm compresses and massage of the eyelid are a usual first step but this alone is often not curative.⁷ Antiinflammatory therapy with topical corticosteroid drops can reduce inflammation but the chronic granulomatous nature of the inflammatory response may not completely resolve with topical therapy. Intralesional steroid injection has been advocated to reduce inflammation.^7–9 In recalcitrant cases, evacuation of the chalazion by surgical incision and curettage is necessary.¹⁰ Randomized controlled clinical trials have been published that compare efficacy and safety of treatment options and show that treatment with intralesional steroid is as effective as incision and curettage (84 % versus 87%, respectively) in contrast to the conservative management with hot compresses, that resulted in only a 46% resolution.^8,9

Repeatedly recurrent or unusually irregular lid lesions mimicking chalazion can be more difficult to diagnose and can certainly be more dangerous, as they are neoplasms of the meibomian gland. It is, therefore, wise to submit curettage specimens for histopathological evaluation in recurrent or unusual circumstances. Sebaceous cell carcinoma is the most worrisome lesion to be identified, but intratarsal keratinous cysts are also an uncommon etiology of a lesion mimicking chalazion.11,12

Meibomian gland dysfunction is probably the most common affliction of the meibomian glands and the pathophysiology is amply described in the MGD Report of 2011.¹ Obstruction of the meibomian gland orifice by keratinized epithelium or thickened abnormal secretion is the primary initiating pathological event.^1,13 Therefore, relief of obstruction is a central goal of therapy. The obstruction of the meibomian gland orifice can be visualized in many cases of MGD but as Blackie, Korb and others have emphasized, nonobvious obstruction is frequent and expression of the eyelid glands as part of the physical examination is essential to diagnosis (Fig. 10.6).¹⁴ Including expression of the meibomian glands as part of the routine evaluation of the eyelids during an eye examination, is a pivotal recommendation of the MGD Report. Mechanical options for treatment typically begin with application of warm compresses, two or more times daily, followed by firm massage of the eyelids.¹⁵ A variety of techniques have been advocated but one effective, simple approach is well described.¹⁵ Other techniques are described in the MGD Report.¹⁶ Warming of the eyelid has been accomplished by application of a washcloth soaked in hot water, but more elaborate methods have also been described. Heating a washcloth or a potato in a microwave oven has been advocated to provide a lasting heat, but overheating can occur and lead to burns of the facial skin.¹⁷ Reports from the Japanese literature describe heating of the eyelids with an infrared lamp, applied as a controlled mask.¹⁸ The application of warm, moist air or steam has also been evaluated.¹⁹ A novel approach to application of controlled temperature concurrent with mechanical expression of the eyelids is the Lipiflow™ system, which utilizes pulsed compression of the eyelids during continuous monitored thermal control (Fig. 10.7).²⁰

Figure 10.6 Expression of the meibomian glands by cotton-tipped swab pressed on lower eyelid. (Reproduced with permission of Elsevier from Foulks GN, Bron AJ. Meibomian Gland Dysfunction. A Clinical Scheme for Description, Diagnosis, Classification and Grading. The Ocular Surface 2003;1:107–26.)

Figure 10.7 (A) Illustration of the Lipiflow™ System that provides monitored temperature warming and intermittent pulsation of the eyelids. (Courtesy of Tear Sciences, Inc; Morrisville, North Carolina.) (B) Cross-sectional view of Lipiflow™ System when applied to eyelid. (www.tearscience.com/physician/in-officeprocedure/lipid-science (accessed Jan., 2013) )

Meibum is a complex mixture of various polar and nonpolar lipids containing cholesteryl esters (CEs), triacylglycerol, free cholesterol, free fatty acids (FFAs), phospholipids, wax esters (WEs), and diesters.21–24 Reported alterations of the behavior and composition of meibum in MGD are summarized in Table 10.1. Changes in the composition and behavior of the meibomian gland secretion (meibum), occurring both with age and due to meibomian gland dysfunction, have been documented by a variety of spectroscopic techniques.^38,39 These studies reveal that abnormal behavior of the secretion is due to increased viscosity, resulting from an elevated phase transition temperature that correlates with a higher degree of ordering of the lipid molecules (Fig. 10.8).⁴⁰ These abnormal properties of the altered meibum can be reversed with several pharmacological therapies (Fig. 10.9).^4,41–43 Tetracycline-class drugs (tetracycline, doxycycline, and minocycline) have been shown to alter the abnormal meibum, presumably by interfering with lipase enzymes that degrade the normal lipids into smaller diglycerides.⁴ Doxycycline has been shown to produce a number of other changes in lipid composition and the presence of caratenoids in the meibum.³⁹ Azithromycin applied topically to the eye and eyelid over a month of therapy is a very effective agent to restore lipid behavior towards normal (Fig. 10.9).^41–43 The effect is probably due to a combination of antilipase activity and anti-inflammatory activity as well.⁴⁵

Table 10.1

Behavior and Composition Changes in Meibum with MGD

Behavior
Increased phase transition temperature	Borchman, et al. (FTIR)²⁵
Increased ordering of lipid	Foulks, et al. (FTIR)²⁶
Increased viscosity	Borchman, et al. (FTIR)²⁵
Composition
Reduced cholesterol	Mathers, Lane²⁷
Reduced triglycerides	Mathers, Lane²⁷
Reduced polar lipids (PE, SM)	Shine, et al.²⁸
Increased lipid peroxides	Augustin, et al.²⁹
Increased free fatty acids	Shine, et al.³⁰
Increased branched chain fatty acids	Joffre, et al.³¹
Increased triglyceride saturation	Joffre, et al.³¹
Change in diglyceride content	Dougherty, et al.³²
Increased phospholipid unsaturation	Shine, et al.³³
Increased protein content	Borchman, et al.³⁴
Change in saturation of carbohydrate chains	Borchman, et al.¹⁰
Decrease oleic acid content	Shine, et al.³⁵
Decreased cholesteryl esters	Shrestha, et al.³⁶
Decrease in terpenoid content	Borchman, et al.³⁷

FTIR, Fourier transform infrared spectroscopy; PE, phosphoethanolamine; SM, sphingomyelin.

Figure 10.8 Spectroscopic analysis of meibum in MGD. The data is obtained by Fourier Transform Infrared (FTIR) spectroscopy and illustrates the change in lipid ordering (B) as it correlates with phase transition temperature (A) of meibum. The linear plot and 95% confidence limits are shown for values of normal meibum with respect to age. (Reproduced with permission of Investigative Ophthalmology and Vision Science from Borchman D, Foulks GN, Yappert MC, et al. Human Meibum Lipid Conformation and Thermodynamic Changes with Meibomian Gland Dysfunction. Invest Ophthalmol Vis Sci 2011;52:3805–17.)

Figure 10.9 Change in meibum behavior with therapy: topical azasite versus oral doxycycline. Note that phase transition temperature returns towards normal with azithromycin therapy and with a more rapid response than to doxycycline. (Reproduced with permission of Lippincott Williams Wilkins from Foulks, Borchman, Yappert, Kakar. Topical Azithromycin and Oral Doxycycline Therapy of Meibomian Gland Dysfunction: A Comparative Clinical and Spectroscopic Pilot Study. Cornea 2013;32:44-53.)

Finally, control of inflammation is an important part of the therapy of MGD. Although topical corticosteroids are probably the most effective and most rapid method for controlling inflammation, the duration of such therapy is limited by the side effects of elevated intraocular pressure and cataract formation. Topical therapy with cyclosporine avoids those complications with improvement of MGD but the duration of therapy required is longer than steroids.⁴⁶ Supplementation of the diet with omega-3 essential fatty acids may also provide some anti-inflammatory benefit, although there are few controlled clinical trials that verify such a benefit, and measurement of meibum does not demonstrate specific effect on the production or composition of the secretion.^47,48 The recommended doses of omega-3 essential fatty acids vary but it is probably wise to follow the guidelines of the American Heart Association which advise limiting omega-3 supplements to 2 to 4 grams per day, unless under physician observation.⁴⁹

Management of MGD

The management strategies for MGD have been well defined and referenced in the 2011 Report of the TFOS Meibomian Gland Workshop with therapy based upon clinical staging of the disease process and the concurrent effect on the tear film and ocular surface.¹⁶ In brief, the clinical staging of the meibomian gland dysfunction evaluates the degree of obstruction of the gland orifices, due both to the number of glands obstructed and the amount of pressure needed to release expressate from the gland.^50,51 Grading of the character of the meibum is typically done in four categories: clear, turbid, turbid with clumps, and paste (see Fig. 10.4).^43,44 The amount of lid swelling and erythema of the lid margin determines the grading of degree of inflammation.^50,51 Other lid margin changes indicate the chronicity of the MGD, as cicatricial dragging of the orifices posteriorly onto the conjunctiva, telangiectasia of the lid margin, notching of the eyelid at the site of scarred orifices, and loss of eyelashes occur over time and do not resolve with therapy (see Fig. 10.5).^50,51

The Meibomian Gland Workshop recommends grading the meibum quality by assessing each of eight glands of the central third of the lower lid on a scale of 0 to 3 for each gland:

0, clear

1, cloudy

2, cloudy with debris (granular)

3, thick, like toothpaste (total score range, 0–24).

Expressibility is assessed on a scale of 0 to 3 in five glands in the lower or upper lid, according to the number of glands expressible:

0, all glands

1, three to four glands

2, one to two glands

3, no glands.

Staining scores are obtained by summing the scores of the exposed cornea and conjunctiva:

Oxford staining score range, 1–15 ⁵²

DEWS staining score range, 0–33.⁵³

Once the severity level of MGD is determined, an appropriate level of therapy can be selected from the treatment algorithm (Table 10.2).¹⁶ Asymptomatic but evident MGD (stage 1) should prompt education of the patient as to the nature and potential progression of disease and the value of prophylactic lid hygiene and massage. Mildly symptomatic disease with increasing evidence of MGD (stage 2) should be treated. If it is determined that the patient’s diet is deficient in omega-3 essential fatty acids, oral supplementation can also be considered.^47,48 The clinical trials evaluating the effectiveness of omega-3 essential fatty acid supplementation are few, but the anecdotal evidence is encouraging that there is benefit. The optimal dosage has not been determined for MGD therapy but it is reasonable to follow the American Heart Association guidelines that recommend 2000 to 4000 milligrams per day but no more than 4000 milligrams per day without physician supervision.⁴⁹ Use of essential fatty acid supplements in patients taking oral anticoagulants is not advisable, as they may alter coagulation of the blood.

Table 10.2

Treatment Algorithm for MGD

(Adapted and modified from the treatment algorithm of the International Workshop on Meibomian Gland Dysfunction. Geerling G, Tauber J, Baudouin C, et al. The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction. Invest Ophthalmol Vis Sci 2011 Mar 30;52:2050–64.)

If the staging of disease determines stage 2 severity, the use of topical 1% azithromycin solution applied nightly in addition to lid massage after application of warm compress is indicated. It is best to apply a drop of the azithromycin solution into the conjunctival sac and then rub the excess fluid on the eyelid, into the base of the eyelashes. Consideration of oral doxycycline at this stage is also reasonable but if the severity is stage 3, the doxycycline regimen is certainly indicated and anti-inflammatory therapy may also be added as topical corticosteroid drops in the short term with concurrent or subsequent topical cyclosporine therapy for longer-term treatment.

Concurrent with the evaluation of meibomian gland function, evaluation of the ocular surface/tear film effects of MGD needs to be done by evaluation of tear film stability (tear break up time (TBUT) ) and ocular surface staining.51,53 Therapy to stabilize the tear film is generally directed at restoring the lipid layer of the tear film by use of topical lipid-enhanced lubricants used two to four times daily.^54,55 A more recent option to restore the lipid layer stabilizing effect to the tear film is liposomal spray.⁵⁶ If inflammation of the ocular surface is also present, the use of topical steroid drops or cyclosporine is indicated.

The category of ‘Plus’ disease identifies associated problems that can occur as a result of MGD or in association with MGD. Treatments specific for each associated problem are recommended and are listed in Table 10.2.

There are a number of possible options for relieving obstruction of the meibomian glands that have not yet been fully evaluated in randomized clinical trials but which have been reported to provide relief of symptoms by reducing meibomian gland orifice obstructions. The Lipiflow^TM System provides pulsed thermal compression of the eyelids. Cannulation of the gland orifices with a specially designed small-bore needle has been reported to relieve symptoms in 75% of patients with MGD.⁵⁷ Further evaluation of these options in controlled clinical trials is warranted.

The use of topical androgen has also been advocated as there is a growing body of evidence that androgen controls meibomian gland secretion and that reduction of androgen, due to advancing age, menopause in women, or the use of antiandrogen drugs in men undergoing prostate cancer therapy leads to meibomian gland deficiency.⁵⁸ No randomized clinical trials have yet proved that topical administration of androgen reverses MGD.