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Meibomian gland dysfunction: what are we looking at?

Given the complex nature of meibomian gland dysfunction, the aim of this article is to give clear understanding of what the practitioner is looking for in this condition.

Optometrists [COMMUNICATION][CONTACT LENSES][OCULAR DISEASE]

Therapeutic opticians [KNOWLEDGE][OPTIONS][SHARE DECISION MAKING]

Dispensing opticians [COMMUNICATION][OCULAR ABNORMALITIES]

Contact lens opticians [COMMUNICATION][CONTACT LENSES]

1 CET POINT

Introduction

Meibomian gland dysfunction (MGD) is a chronic, debilitating disease, which affects millions of people worldwide. The term posterior blepharitis is synonymous with MGD and is one of the most common disorders encountered in ophthalmic practice. (1) Blepharitis can be divided into: anterior, affecting the lash bearing region; and posterior, affecting the meibomian glands (see Figure 1). Differentiation between the two forms may be overlooked resulting in poor management of the condition.

A main function of meibomian gland secretions is to impede tear evaporation; its other functions include: providing a smooth optical surface; improving tear stability and spreading; preventing tear film contamination; sealing the lid margins during sleep; and preventing tears spilling over the lid margin. (1) In the case of MGD, the amount of meibomian oil (meibum) delivered to the oil reservoir is reduced; this affects tear stability, surface tension and the tear film lipid layer (TFLL) depletes. If the TFLL is disrupted, too much water from the tears evaporates, resulting in evaporative dry eye (EDE). MGD is, therefore, a chief cause of EDE with increased evaporation from the ocular surface, increased staining and ocular surface damage. Over 80% of dry eye patients (as diagnosed with Schirmer's test, osmolality, tear break-up time (TBUT), corneal and conjunctival staining, and ocular surface disease index (OSDI)) may have MGD signs. (2)

Histology of healthy meibomian glands

Meibomian glands are modified sebaceous (sweat) glands. Circular sacs (acini) containing meibum-secreting cells are attached along the length of the duct. These cells disintegrate to release meibum, which travels along the duct by mechanical forces with each blink. The secretions contain a mix of phospholipids, cholesterol, wax and cholesterol esters and small amounts of hydrocarbons, triglycerides and triglycerols. (3)

Meibomian glands are arranged in regular intervals with their orifices opening onto the lid margin just anterior to the mucocutaneous junction. (4) This position allows the meibum to be released into the marginal reservoir where it is spread by the lids onto the anterior surface of the tear film. There are approximately 30-40 glands in the upper lid and 20-30 in the lower lid. (1) In the centre of the eyelid the ducts are at their longest approximately 5.5mm long in the upper and 2mm in the lower lid. (5)

Approximately 45% of adult glands are active at one time; at age 20 an average of 14.5 glands could be expressed in the lower lid, but this reduces to seven by the age of 80. (6) It is theorised that glands go through cycles of activity, followed by inactivity during which the acinar supplies are replaced. (3) The nasal glands are most active, followed by the central third with least activity in the temporal lid area. (3)

Putting the D in MGD

MGD can be diagnosed into various forms:

* Congenital, such as when meibomian glands are absent or are replaced by an additional row of lashes (distichiasis) (1)

* Acquired, which can be further divided into:

** Hypersecretory--release of large volumes of oil and occurs in 100% of cases of seborrhoeic dermatitis and can also occur in acne rosacea

** Hyposecretory--reduced secretions

** Obstructive--the most common form of MGD, which may be classified as: simple (hyperkeratinisation) with excessive development of keratin in the epidermis leading to duct occlusion in the form of plugging or pouting; cicatricial (scaring/formation of new connective tissue following wound healing).

MGD can be symptomatic or asymptomatic and may be focal, affecting scattered glands, or diffuse, affecting the glands as a whole to some extent. The condition can be primary or secondary with the latter commonly associated with skin conditions. The condition may also be classified as: cicatricial or non-cicatricial; inflammatory, as in meibomitis (common causes of which include blepharitis and acne rosacea) or non inflammatory. (3) Table 1 and Figure 2 show several of the features of MGD. With age, a lot of changes occur within the meibomian glands including: narrowing/ plugging of the orifices; vascularity; keratinisation; appearance of telangiectasia; lid margin rounding; increased prevalence of blepharitis; and reduction in the number of glands secreting oil. (7)

Meibomian gland dropout refers to partial or complete loss of acinar tissue in meibomian glands. Meibomian gland dropout in contact lens wearers within their 30s has been found to be similar to that of normal 80 year olds; (8) this suggests that contact lens wear speeds up the normal ageing process of meibomian glands, although the pathophysiology is unclear.

Timeline

The literature suggests that pathology of the disease starts with obstruction by hyperkeratinisation, accumulation of cell debris or increased meibum viscosity. (9) Causes of hyperkeratinisation include: increasing age; hormone disturbances; toxicity from medication; contact lens wear; and skin diseases such as acne rosacea. (5-9) When the orifice is blocked, meibum accumulates in the duct. Due to the continuation of the acini to produce meibum, the pressure builds in the glands, first resulting in dilation of the ducts. The pressure is then relayed to the acini causing them to undergo atrophic changes. Secondary hyposecretion occurs, followed by gland dropout. (5) The prevention of meibomian oil expression results in tear film instability, increased evaporative dry eye, hyperosmolarity and ocular surface irritation. (9)

MGD first goes through an asymptomatic stage, like most disorders, and may go unseen by a clinician. For this reason it may be advisable to assess quality and quantity of expressions in routine testing.

The International Workshop on Meibomian Gland Dysfunction recognises obstructive MGD as the most common cause of EDE; (3) it regularly occurs without any signs of anterior blepharitis and minimal lid inflammation meaning it is often overlooked. When a patient presents with dry eye symptoms, performing diagnostic expression is recommended. (3) This can be done by applying moderate pressure with a fingertip, cotton tip or glass probe, as well as special tweezers, (10) to the centre-third of the lower lid.

It is suggested that pressure should be maintained for 10 to 15 seconds as it takes 12 seconds for the gland to fully empty, (11) and if four of the six to eight central glands secrete meibum the likelihood of dry eye symptoms is low. (10) Korb and Henriquez found that in asymptomatic patients gentle pressure was enough to express clear oil, (3) yet some asymptomatic patients expressed creamy or thick material when forceful expression was applied. Since early stage treatment is quite straightforward, intervention while the disease is asymptomatic would be beneficial.

However, in the absence of symptoms, patient compliance may be poor. Other options for treatment other than warm compress and lid hygiene, which practitioners can incorporate into a dry eye work-up, include debridement of the meibomian gland orifice, meibomian gland expression and removal of blepharitis crusts. (12)

MGD quantification techniques in clinical practice

Techniques for evaluating the presence and severity of MGD in practice include:

* Clinical history and symptoms

* Expressibility: the number of glands that secrete oil under digital pressure to those which do not. In normal lids, light digital pressure should excrete clear oil; heavy pressure may be needed to express thicker meibum (3)

* Marx line (ML) runs along the inner eyelid margin seen after instillation of fluorescein, lissamine green or rose Bengal. (13) In normal eyes ML is found on the conjunctival side of the meibomian gland orifices (see Figure 4)

* Meibography is used to measure gland drop out and is usually the last test to be performed as it is invasive. The lid is everted and the glands are transilluminated, usually with infrared light and photographed. This can be achieved with a camera mounted onto the slit lamp or a dedicated meibographer (see Figure 5)

* Secretion quality: clear, cloudy, toothpaste consistency

* Slit lamp examination includes rounding, thickening, hyperkeratinisation, vascularity, notching, placement of mucocutaneous junction, pouting, plugging, capping, duct exposure

* Tear break-up time to assess tear stability.

Regulation of the meibomian glands

There is a dense structure of nerve fibres surrounding the acini; neural regulation includes sympathetic and parasympathetic innervation. (5) It is also thought that meibomian glands are regulated by hormones, with both androgen and oestrogen receptors found in these glands. (1) Indications from animal studies are that hormonal changes can increase meibum viscosity, which may be a cause of obstructive MGD, eventually resulting in gland dropout. (5)

In the skin, androgens stimulate sebaceous secretion so it is thought that they also stimulate secretion of the meibomian glands. (14) Increased signs and symptoms of dry eye and MGD have been found in patients on antiandrogens (such as in prostate or breast cancer treatment) and in women with complete androgen insensitivity syndrome (CAIS). (15-17) Topical administration with androgens (including testosterone ointment or the central glands are very short eye drops) in several studies has shown improved tear quality, including increased break-up time and lipid layer thickness. (18-24) This suggests that androgens have a positive effect on meibomian gland function by modulating meibomian gland secretions.

There is less understanding about the effect of oestrogens on meibomian glands than there is about androgens. Oestrogen is thought to have the opposite effect of androgens by reducing secretion and promoting inflammation. (5) However, oestradiol ointment applied to the conjunctiva has been associated with improvements in TBUT. (25,26) The influence of sex hormones on EDE and the meibomian gland are yet to be elucidated.

Conclusion

Recognising and understanding the signs of MGD is important to be able to correctly diagnose as well as grade the condition in order to establish if disease is progressing or responding to treatment. This helps the understanding of treatment efficacy, patient compliance and possible future complications, such as contact lens drop out or delayed surgery/post-surgery complications. When discussing treatment it is essential to discuss the long-term nature of MGD management and to encourage patients to include lid maintenance measures in their daily routine.

Acknowledgements

The authors and publishers acknowledge the University of Iowa and EyeRounds.org for permission to reproduce this copyrighted material from webeye.ophth.uiowa.edu/ eyeforum/atlas/index.htm

Exam questions

Under the enhanced CET rules of the GOC, MCQs for this exam appear online at www.optometry.co.uk. Please complete online by midnight on 13 May 2017. YYou will be unable to submit exams after this date. Please note that when taking an exam, the MCQs may require practitioners to apply additional knowledge that has not been covered in the related CET article.

CET points will be uploaded to the GOC within 10 working days. You will then need to log into your CET portfolio by clicking on 'MyGOC' on the GOC website (www.optical.org) to confirm your points.

References

Visit www.optometry.co.uk, and click on the 'Related CET article' title to view the article and accompanying 'references' in full.

Course code: C-55547 Deadline: 13 May 2017

Learning objectives

* Be able to explain to patients about meibomian gland dysfunction (Group 1.2.4)

* Be able to identify and manage cases of meibomian gland dysfunction in contact lens patients (Group 5.2.1)

* Be able to recognise the signs and symptoms of meibomian gland dysfunction and manage the patient accordingly (Group 6.1.4)

* Be able to explain to patients about meibomian gland dysfunction (Group 1.2.4)

* Understand the management of patients with meibomian gland dysfunction (Group 8.1.3)

* Understand the natural progress of meibomian gland dysfunction and be able to assess its severity

* Be able to consider the treatment options for meibomian gland dysfunction (Group 2.1.6)

* Be able to discuss the options for managing meibomian gland dysfunction (Group 3.1.7)

* Be able to explain to patients about meibomian gland dysfunction (Group 1.2.4)

* Understand the management of patients with meibomian gland dysfunction (Group 8.1.3)

* Be able to explain to patients about meibomian gland dysfunction (Group 1.2.4)

* Be able to identify and manage cases of meibomian gland dysfunction in contact lens patients (Group 5.4.1)

Emma Gibson BSc (Hons)

* Emma Gibson graduated from Aston University and is currently doing her PhD at the University of New South Wales in Sydney, having worked in practice in North Wales for several years. Emma's research involves investigating associations between sex hormones and dry eye/MGD. Part of her research involves the development of a time efficient MGD grading scale for use routinely in clinical practice.

Caption: Figure 1 Slit lamp photo of the lower eyelid showing irregular eyelid margin/notching (long arrow) and meibomian gland orifices (short arrows)

Caption: Figure 2 Slit lamp photo showing telangiectasia (arrow) on the lower eyelid. Anterior blepharitis crusting is also present on the eyelashes

Caption: Figure 3 Slit lamp photo of a capped meibomian gland on the lower eyelid (arrow). Anterior blepharitis crusting is also visible along the base of the eyelashes

Caption: Figure 4 Slit lamp photo showing lissamine green staining of Marx line (ML) along upper and lower eyelids. The nasal and central portions are grade 1 (Ml) where ML touches orifices in parts, and the temporal portion is grade 2 (M2) where ML runs through the meibomian orifices

Caption: Figure 5 Infrared images of everted top and bottom eyelids (meibography) of a patient with severe meibomian gland disease. The nasal and temporal glands have completely dropped out due to atrophy caused by stress to the meibomian glands, whereas
Table 1 Features of MGD

Lid margin    * Rounding of the posterior margin interferes with the
              normal placement of the lid against the globe

              * Thickening of the lid margin is a common feature but
              difficult to measure due to the rounding of the anterior
              margin. It has been suggested to measure from the
              posterior margin to the posterior lash line since these
              features are relatively constant (3)

              * Hyperkeratinisation is observed as increased
              reflectance of the skin at the marginal lid, frequently
              seen with facial eczema. It is a major cause of orifice
              obstruction and causes atrophy of the gland, without
              inflammation (5)

              * Increased vascularity, more than is normal with age

              * Irregular lid margin associated with reabsorption of
              skin in areas of gland loss, for example, notching (4)
              (see Figure 1)

              * Telangiectasia is observed as visibly dilated blood
              vessels on the lid margin, appearing as small red or
              purple clusters which increase with age, significantly
              more common in the lower than upper lid in the elderly
              (1) (see Figure 2)

Mucocu-       * Anteroplacement or retroplacement of the mucocutaneous
taneous       junction (MCJ). Anteroplacement: the junction moves
junction      forward making it appear that the orifices lie in mucosal
              tissue (3)

              * Retroplacement: the MCJ moves posteriorly,
              keratinisation of the posterior lid margin occurs;
              retroplacement is more common than anteroplacement. The
              gl"ands may or may not move, although frequently at this
              late stage the glands are not functioning

Orifices      * Reduction in the number of functioning orifices

              * Pouting or elevation of the gland is an early sign of
              MGD; the gland is plugged with accumulated excreta

              * Capping of the gland by a dome of oil (see Figure 3)

              * Narrowing of the orifice so that the punctum is no
              longer visible and oil cannot be expressed

              * Duct exposure so that it is visible at the surface

Secretions    * Expressibility of secretions with applied pressure to
              the lid margin

              * Normal secretions are clear; however, in MGD they can
              be cloudy, thick, even a toothpaste-like consistency
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Author:Gibson, Emma
Publication:Optometry Today
Date:Apr 1, 2017
Words:2575
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