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Contact us at email@example.com Chapter 7 Dry eye — An Insight into Meibomian Gland Dysfunction Vikas Tah, Kamran Saha, James Myerscough, Muhammad Ahad, Jason Ho, Pranev Sharma, Farihah Tariq and Stephen Tuft Additional information is available at the end of the chapter http://dx.doi.org/10.5772/58566
1. Introduction The term ‘Dry Eyes’ was first coined in 1950 by the Ophthalmologist Andrew De Roeth (1893– 1981): a dacryologist who introduced the term dry eye. For decades it was thought dry eyes was limited to a reduction in the aqueous phase of the tear film. It was as recent as 1995 that dry eyes was eventually recognised as a multifaceted ocular pathology which was due to decreased tear production and increased tear evaporation . In this chapter we will focus on the latter, specifically looking at meibomian gland dysfunction.
An estimate of the prevalence of dry eyes is difficult given that many sufferers may be asymptomatic or dismissive of subjective questionnaires of their symptoms if mild. Various studies estimate the prevalence as between 7.4% to 33.7% [2-3]. The epidemiology of dry eye depends on the mode of diagnosis, population surveyed and study cited.
Large American epidemiological studies estimate symptomatic dry eyes to affect 7% of women and 4% of men over the age of 50 years in the United States . Similar data is seen in Australian studies . The far eastern studies report the largest proportion of dry eye sufferers with Taiwan having the highest at 33.7%  followed by Japan and Indonesia .
2. Meibomian gland dysfunction Themeibomian glands, named after the German physician Meibom in 1966, are specialised sebaceous glands within the eyelids. They number 20-5 on the lower lids and up to 50 on the upper lid. Meibomian glands are responsible for secretion of a lipid rich mixture call meibum onto the tear surface through small openings found on the lid margin. A single gland consists of a central duct linked to multiple acini via ductules. Meibum is loaded into acini and released © 2014 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
156 Ophthalmology - Current Clinical and Research Updates into the central duct where it moves to the openings on the lid margin and ocular surface. The glands undergo constant renewal and are delicate owing to their holocrine nature.
Scheme 1. Diagram courtesy of International Workshop on Meibomian Gland Dysfunction It is widely thought that reduced meibum quality and quantity in addition to hyperkeratini‐ sation of the ductal epithelium are the main reasons for meibomian gland dysfunction (MGD).
Hyperkeratinised ducts and thicker meibum secretions lead to obstruction of the ducts. A progressive increase in pressure from continuous meibum secretion causes widening of the duct, acinar atrophy with cornification of duct epithelia. Ultimately there is reduced meibum secretion and gland drop out causing an unstable tear film.  The tear film lubricates the ocular surface, which is vital to its maintaining its function and well being. It also forms a vital role in light refraction in the air-tear-cornea interface. Tear film is structured into 3 primary layers: The inner layer comprises mucin and a layer of glycocalyx that is synthesised by the conjunctiva and epithelial cells. The lacrimal gland primarily secretes the middle aqueous layer. The outermost lipid layer is secreted by the meibomian gland. This superficial layer stabilises the tear film by preventing its evaporation. Meibomian gland dysfunction is the most common cause of evaporative dry eye. Left untreated dry eye initially causes irritating ocular surface symptoms and signs that can threaten visual impairment, cause corneal perforation and blindness. Dry eye — An Insight into Meibomian Gland Dysfunction 157 http://dx.doi.org/10.5772/58566 (courtesy of Stoke Mandeville Hospital) Figure 1. Lower lid meibomian glands Broadly meibomian gland dysfunction can be defined 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[9-10].
Meibomian gland dysfunction can affect many different groups.
Age is a major risk factor for the development of MGD. It is more common in the elderly.
Studies in humans seem to mirror the effects in animals . Decreased acinar prolifera‐ tion, atrophy and altered localisation of the lipogenesis factor PPARγ (regulates meibo‐ mian differentiation and secretion) are seen in mice. Elderly patients have been noted to have a higher rate of meibomian glad dropout [10-11] with half as many functioning glands between 20 to 80 years of age. Human cadaveric studies show gland orifice metaplasia and narrowing [12-13] with hyperkeratinisation and lipogranulomatous inflammatory changes.
Additionally meibum composition changes with age yielding a reduced volume and increased viscosity [10-14].
Androgens are known to be integrally involved in differentiation of sebaceous glands all over the body and have been shown to promote genes essential for meibomian function [13-14] Furthermore, complete androgen insensitivity syndrome has been shown to have altered meibomian glands and composition of lipid secretions that resulted in clinically apparent signs and symptoms of MGD [15-16].
Confusingly, chronic blepharitis has been suggested as a cause for MGD. Whilst MGD itself is a cause of chonic blepharitis, there is considerable overlap with other causes of chronic blepharitis that may accentuate MGD. One study showed 74% (42 of 57) chronic blepharitis 158 Ophthalmology - Current Clinical and Research Updates sufferers had evidence of meibomian gland loss on meibography whereas 20% (4) of matched normal patients had any dropout. More detailed understanding is needed regarding the overlap of MGD with chronic blepharitis [18-19].
Figure 2. Lower lid meibomian glands and dropout in an elderly patient (courtesy of S Tuft) Figure 3.
Meibum secretions of elderly patient showing increased plugging and viscosity (courtesy of S Tuft)
fibroblasts and plasma cells which may thus offer a potential explanation for refractory and recurrent chalazia in some patients.  Figure 4. Desmodex infested lashes with meibomian gland dysfunction Contact lens wear can increase the risk of MGD. Studies utilising meibography have shown that contact lenses alter meibomian gland morphology with greater rates of dropout than noncontact lens wearers. The duration and type of contact lens was weakly associated with this.
By inserting and removing contact lenses, desquamated epithelial cells have been shown to obstruct the duct orifice leading to stagnation and atrophy [22-23]. While some studies show a statistically significant increase in MGD in contact lens wearers [22-24] others did not show significant differences [25-26]. It is important however to bear in mind these studies defined meibomain gland dysfunction differently. Damage to stem cells at the limbus is likely to be different based on duration on contact lens wear and may help account for the differences.
Environment may play a role in MGD. It is likely that factors such as temperature, humidity and visual undertaking have an accentuating impact rather than develop MGD. For example, concentrated computer use may be associated with reduced blink rate, exacerbating symptoms of MGD. One study of 70 patients found 74% of video display terminal users had MGD .
Decreased conjunctival temperature has been suggested to cause obstructive MGD through increased meibum viscosity [28-29].
Various medical conditions have been associated with MGD. Polycystic ovary syndrome (PCOS), where there is often insulin resistance and hyperinsulinaemia can result in increased androgen synthesis. Androgen receptors have been found in meibomian glands with a possible effect on function [30-33]. Twenty two (22)% of PCOS patients had MGD compared to 13% of normals in one study .
Dyslipidaemia appears to be associated with MGD. Patients with moderate to severe MGD have a higher incidence of dyslipidemia with respect to elevated total cholesterol than the general population [35-36]. Higher meibomian cholesterol ester levels are associated with MGD in humans .
160 Ophthalmology - Current Clinical and Research Updates Sjorgen’s syndrome has been shown to have a higher incidence of MGD. One study found a higher incidence of MGD in MGD related dry eye to other causes of dry eye. The actual association, whether causative or a consequence of dry eye is not established and further study is needed [38-39] Multiple medications have been implicated as possible risk factors for MGD. Studies looking at the acne treatment isotretinoin, 13-cis retinoic acid, have found that this resulted in altered meibum secretion, atrophy of the gland, reduced tear break up time and dry eye symptoms [40-41]. Other studies have looked at medication under the umbrella category of dry eye, not specially MGD. There may however be some overlap with MGD. Included in this category are antihistamines. One study has shown that treatment of allergic conjunctivitis with once daily loratidine resulted in signs of ocular dryness [42-43].
Post-menopausal hormone therapy has been associated with MGD [44-47] although the pathophysiology is not fully understood. Whilst established that sex hormone levels change from pre-to post-menopause, it is presumed that PMH results in changes to meibum gland secretions that can lead to MGD. Higher estrogen levels post-menopausally have been implicated in reduced tear function . The largest of the studies, looking at 3500 patients from the Blue Mountain Study has shown a statistically significant 60% higher prevalence of dry eye in PMH users. A longer duration of use has been associated with longer symptoms .
Anitidepressant use has been associated with a higher risk of evaporative dry eye symptoms.
Often many such medications simply have visual blurring only as a side effect without any mention of dry eye disease [48-51].
Omega 3 oils have been shown to have a beneficial effect on MGD whilst omega 6 oils have an opposite effect. Both are essential for growth and development. The omega 3 oils are found naturally in Mediterranean diets, flaxseed and cod liver oil . Omega 6 oils are found typically in Northern European diets containing high red meat and less of the above . The most detailed study to date showed a reduction in meibum thickness, dry eye signs and tear break up time in those with a high omega 3 to omega 6 ratio , agreeing with previous findings [52, 54. 55]. These oils compete for an enzyme involved in the inflammatory path‐ waytherefore it is the ratio of omega 3 and 6 that is crucial. The ideal omega 6:3 ratio is 4:1 but typical Northern European and American diets are in the realm of 14:1 A higher omega 6 to 3 ratio results in overproduction of pro-inflammatory PGE2 from omega 6 and underproduction of anti-inflammatory PGE1 and PGE3 via omega 3 that induces MGD .
described. It is important to ask what time of day this occurs to try to distinguish from other causes of dry eye. Blepharitis is typically worse in the morning with redness, crusting, puffiness, itchy lids or a ‘gritty sensation’ within the eyes.
5. Clinical assessment There are different ways to assess meibomian gland dysfunction. Whilst a slit lamp is certainly beneficial and the commonest form of assessment, one can simply use a direct ophthalmoscope for those in primary care settings. Though it does not give as detailed a view the principles are the same as for slit lamp examination. The key is to observe the meibomian glands and ocular surface. With the ophthalmoscope one needs to place on high magnification to view the state of the meibomian glands which are located posterior to the greyline Often orifices can be seen to be plugged, or pouting. Surrounding tissue can be erythematous with telangiectatic vessels.