Meibomian Gland Disease. Classification and Grading of Lid Changes

Eye (1991) 5, 395--411

Meibomian Gland Disease. Classification and Grading of Lid Changes

A. J. BRON, L. BENJAMIN, G. R. SNIBSON Oxford

Summary In recent years attention has been paid to meibomian gland dysfunction (MGD) as a distinct clinical entity responsible for chronic symptoms and signs and occurring independently or in association with atopy, cicatrising mucosal disorders and rosa­ cea. Attempts to correlate MGD with microbiological and lipid biochemical changes are confounded by the absence of a clear descriptive language for the disorder and its associated changes. Such a language is crucial for the conduct of cross-sectional and natural history studies and therapeutic clinical trials. We present a comprehensive classification and grading scheme of meibomian gland disease, supporting our obser­ vations with illustrations.

Meibomian gland disease (MGD) is common mucous membrane of the tarsal conjunctiva, and sometimes responsible for severe and while the anterior three quarters is skin. The chronic symptoms and secondary conjunctival anterior margin is less sharply rounded and its and corneal changes. The purpose of this anterior half bears multiple rows of lashes. paper is to review its components, with par­ The meibomian gland orifices emerge just ticular attention to definitionand illustration. anterior to the mucocutaneous junction, which runs as a smoothly curving line, parallel Normal Meibomian Gland Anatomy and to the posterior margin, from one end of the Physiology lid to the other (Fig. 1a). This cutaneous The most anterior zone of the tear film is the location is essential for the delivery of lipid lipid layer which derives from oil secreted onto the anterior face of the tear film. The onto the lid margin by the meibomian glands, ductal lining is composed of keratinised and layered onto the surface of the preocular squamous epithelium. Jester et al. have sug- tear film with each blink. The functions of Table I. Functions of meibomian lipid meibomian oil are listed in Table I. The normal lid margin, measured from its 1 Reduction of evaporation from the Meibomian posterior border to the posterior lash line is preocular tear film 2 Enhancing tear film stability by lowering surface approximately 2.5 mm wide in the adult and tension presents a smooth fiatsurface whose posterior 3 Prevention of spill-over of tears from the lid margin margin is sharply rounded at about a right 4 Prevention of contamination of the tear film by angle, to conform to the surface of the globe. sebum 5 Scaling the apposed lid margins during sleep Theposterior quarter consists of the marginal

Correspondence to: Professor A. J. Bron. FRCS.. FCOphth. Nuffield Laboratory of Ophthalmology. Walton 'itreet, Oxford, OX2 6AW. 396 A. J. BRON ET AL.

gested, on the basis of immuno-histochemical The meibomian glands are tubulo-acinar studies that keratinisation is partial, i.e. less and their mode of secretion is holocrine, that than that of the neighbouring skin. 1 is, the contents of the secretory cell are lost in There are about 30-40 glands in the upper the process of secretion. The stimulus to tarsus, and fewer, (20-40) in the lower. The secretion is not fully known. It is assumed that fine orifices of the main ducts are flush with the secretion of meibomian oil is modulated the surface and visible on biomicroscopy by the levels of plasma sex hormones, since (Fig. Ib). In youth, each orifice exhibits a the meibomian glands are modifiedsebaceous number of concentric circular zones. These glands and the role of the sex hormones in are: modulating sebaceous secretion is well (1) a central punctum surrounded by an known. Thus androgens such as testosterone opaque cuff, increase, and oestrogens or anti-androgens (2) a dark or translucent ring, (e.g. cyproterone acetate) reduce secre­ (3) a further opaque cuff. (Fig. 2). tion.2-5 This information is not available for The inner cuff is assumed to be the keratini­ the meibomian glands. However, there is an sed lining of the duct and the translucent zone association between meibomian gland disor­ the surrounding dermis. The outer, cream­ der and seborrhoeic eczema on the one hand coloured cuff is thought to be subepithelial, and the latter condition and androgens on the since it is absent from pigmented skin, where other which suggests that androgen levels may the epithelial pigmentation may obscure the at least influence meibomian gland function.6 outer cuff completely (Fig. Ic). The cuff may The meibomian glands have a rich innerv­ therefore be formed by a dermal or subdermal ation but this has not been fully investigated. structure such as the muscle of Riolan or the Hartschuh et al. have demonstrated VIP-ergic distal tip of the Meibomian acinus. This innervation of human meibomian glands.) requires histological demonstration. The mei­ Adrenergic and cholinergic innervation does bomian glands were first clearly described by not appear to have been studied, but it is of Heinrich Meibom.'b interest that an increase in secretion occurs In youth and in young adults the intermar­ after experimental section of the cervical sym­ ginal surface is relatively avascular. The papil­ pathetic in laboratory animals.H Also, a lary vasculature of the mucosa is visible in relationship between meibomian gland young lids, and with age a vascular architec­ obstruction and epinephrine use has been ture identifies itself increasingly on the cuta­ documented thoroughly in the experimental neous margin. Most characteristic of these is model. 9-11 It is however not known whether the vascular network which reaches the edge this is a toxic effect of the drug or an of the outer cuff of each meibomian orifice, expression of adrenergic action. The features and the venous network which ha.s a segmen­ of epinephrine-induced MGD are: plugging tal distribution between the orifices, and of and an increase in the level of epithelial whose tributaries arise from the mucosa at the keratinisation of ducts; cystic dilatation of muco-cutaneous junction. They pass forwards ducts and acini, and secondary compression in the dermis of the cutaneous margin, receiv­ or atrophy of acinar cells. ing branches from the pretarsal zone at the Meibomian oil is liquid at lid temperature. level of the grey line. Its melting point range is-19.5-32.9°C.'2 The The macroscopic architecture of the meibo­ mechanical action of the lids is regarded as mian acini is visible through the tarsal con­ important in the delivery of secreted lid oil junctiva. The acinar lobules on either side of onto the tear film.'3a.b 'Jetting' of lid oil at the the central main duct are distinctly visible as orifices just following a blink, has been yellow, grape-like clusters (Fig. Id). With reported, 14.15 which would support such a view age, the visibility of the glands diminishes and but would also be in keeping with secretion by they ultimately cannot be seen. This is other mechanisms. Tiffany discusses the assumed to be due to increasing opacity of the forces which are brought to bear by lid submucosal connective tissue and the tarsal closure. 16 plate itself. A full account of meibomian lipid com· MEIBOMIAN GLAND DISEASE 397

Fig. lao Normal lid margin: Male: 12 years cutaneous Fig. ld. Normal tarsal plate: Male: Age 24 years. part seen in specular reflection. Mucocutaneous Acini seen through conjunctiva. junction arrowed.

Fig. lb. Normal lid margin. Male: Age 25 years. Fig. Ie. Chronic Meibomitis. Adult male. West Normal Meibomian orifices, in this case disposed in an Indian. Lower lid everted to show rounding of posterior irregular manner anteroposteriorly. Grey line arrowed. lid margin.

Fig. Ie. Norma/lid margin. Pigmented: West Indian Fig. If. Meibomitis: Increased vascularity of the lid adult female. Only the punctum and inner cuffs of the margin. Meibomian orificesare seen. The dermal ring and outer cuffare obscured by epithelial pigment. 398 A. J. BRON ET AL.

Fig. lg. Meibomitis: 'Hyperkeratinisation' of the Fig. lj. Ridging at the mucocutaneous junction, cutaneous part of the lid margin. running between an irregular row of Meibomian orifices.

Fig. lh. Meibomitis: Irregularity of the posterior lid Fig. lk. Capping of a Meibomian orifice. The margin. neighbouring orifices are relatively normal.

Fig. Ii. Severe Meibomitis in a patient with atopic Fig. 11. Meibomitis: Pouting of 2 adjacent orifices keratoconjunctivitis Retroplacement of the (viewed in profile). mucocutaneous junction: The squamous metaplasia is well behind the irregular row of Meibomian orifices (arrow heads). MEIBOMIAN GLAND DISEASE 399

Fig. 1m. Opaque Meibomian orifices. Those on the Fig. 10. MGD: Opaque obliterated Meibomian left side of the picture are retroplaced. orifices.

Fig. In. Severe MGD: The central orifices(arrowed) Fig. Ip. Globular degenerative changes seen at the lid are opaque, and retroplaced. Adult patient with margin and resembling spheroidal degeneration. longstanding atopic kerato conjunctivitis.

Fig. Iq. Atopic keratoconjunctivitis: Periductular fibrosis.

posItIon is given by Tiffany;16 There are Meibomian Gland Disease earlier reviews by Tiffanyl7 and Nicolaides.l� Meibomian gland diseases are common, and Anatomical accounts are given by Virchow ,19 some may be associated with systemic Duke Elder,20 Wolfel and Murube.22 disease. Meibomian gland dysfunction 400 A. J. BRON ET AL.

___ Meibomian orifices ____-,.--- ______--,

Mucous membrane mcj

Marginal skin

Lashes

Fig. 2. Diagram of the Meibomian orifices and mucocutaneous junction of the lid margin.

(MGD) is a portmanteau term for conditions (a) A congenital deficiency of meibomian such as meibomian seborrhoea and meibom­ glands was reported in an otherwise normal itis. A list of diseases is illustrated in Table II. 16-year-old girl who presented with contact The features of meibomian gland disease are lens intolerance, interpalpebral staining and discussed, and a classification and grading reduced break up time (BUT).21 She showed scheme for MGD is given. bilateral absence or hypoplasia of upper and lower glands, with a reduced number of ori­ 1. Absence and Deficiency fices. Glands were stunted or rudimentary Absence or deficiency of the meibomian and some gland rudiments were not associ­ glands may be congenital and are character­ ated with a meibomian orifice. Other glands ised by an absence or reduced number of ori­ of more normal length were obliquely dis­ fices at the lid margin. Rudimentary glands posed in the lid; oil could be expressed from may be seen as yellow streaks through the tar­ some but not all glands. We have since seen an sal conjunctival surface or glands may be com­ additional case in which only the lower lids pletely absent. Alternatively, the remaining were affected. glands may be enlarged and elongated with (b) Holly and Lemp described a 21-year-old their proximal portion folded into the hori­ male with anhydrotic ectodermal dysplasia zontal meridian or hooked back in a hairpin and no detectable meibomian gland orifices24 manner. and Baum and Bull, and Mondino et al. each Table II Meibomian gland diseases described a case of ectrodactyly, ectodermal dysplasia, cleft-lip and palate, in which the Absence or deficiency glands were congenitally absent.24.25.26 .Primary: Congenital (c) An unusual meibomian gland abnormal­ Anhydrotic ectodermal dysplasia Ectrodactyly, ectodermal dysplasia, cleft ity was described in a boy with icthyosis in lip and palate whom normal meibomian orifices were pres· Icthyosis ent but in whom pressure over the tarsal .Secondary:to lid disease plates expressed a thick coil of inspissated 2 Replacement .Primary: Dystichiasis material of toothpaste consistency.27 The mei· .Secondary:dystichiasis due to metaplasia bomian 'glands' appeared as cigar-shaped 3 Meibomian Seborrhoea yellow streaks, brigher than normal and lack· 4 Meibomitis ing the usual racemose morphology. It is likely 5 Meibomian neoplasia that the expressed material was not a lipid MEIBOMIAN GLAND DISEASE 401 secretion, but represented keratinised, des­ which are relatively constant features of the quamated, icthyotic material accumulated lid. within the main glandular duct. This would be Rounding of the posterior lid margin is often in keeping with the observation of desqua­ associated with thickening and interferes with mated epithelial cells in the mouths of the the normal apposition of lid to globe (Fig. Ie). ducts demonstrated in MGD.2x-30 Vascularisation increases with age. In MGD An acquired deficiency of meibomian there is an exaggeration of this, and an invas­ glands is frequently encountered in associ­ ion of the outer and then inner cuffs of the ori­ ation with destructive lid disease. It thus fice. (Fig. If). occurs with staphylococcal and atopic ble­ Hyperkeratinisation is an eczematised appear­ pharitis and in forms of cicatrising conjunctiv­ ance of the cutaneous margin, frequently itis such as trachoma, mucous membrane encountered in atopes with facial eczema but pemphigoid and erythema multiforme. Clini­ also in non-atopic subjects. (Fig. Ig). cal features include absent or puckered and Irregularity of the lid margin arises from occluded duct orificesand sufficientcicatricial absorption of tissue, often in the region of disorganisation of the affected portions of the obliterated meibomian orifices but will occur lid to make it impossible to assess the extent of with more gross distortions of lid architecture gland substance present. in cicatricial and ulcerative lid disease. (Fig. Ih). 2. Replacement of Meibomian Glands In dystichiasis, an extra row of lashes takes Mucocutaneous Junction the piace of the meibomian glands. The con­ The factors which maintain the geometry and dition may be partial or complete and may be polarity of the mucocutaneous junction inherited (e.g. as a dominant) or acquired (MCl) of the lid have not been explored but focally as a metaplastic reaction to mucoc­ presumably are the same as those that operate utaneous disease of the lids. at other mucocutaneous junctions. The junc­ tional location and morphology may be 3. Meibomian Gland Dysfunction altered in MGD. The MCl is best identified Meihomian gland dysfunction will be used by its specular reflection. Although the here to imply an affection of the meibomian position of the anterior edge of the tear men­ glands, without necessarily implying that iscus may correspond with it in health, in inflammationis present. It is often associated disease it may not be an accurate guide. with changes in the lid beyond the confinesof (i) Anteroplacement: The junction becomes the glands themselves. This section will deal irregular in MGD. The mucosa may in particular with the individual features of spread forwards, so that the orifices MGD. These are described in relation to appear to lie in mucosal tissue. mucocutaneous changes, changes in the mei­ (ii) Retroplacement: Here, there is a pos­ bomian orifices, ducts, and acini and the terior movement of the MCl, with a secretory' performance of the gland. spreading, keratinising squamous meta­ Features are described topographically to plasia of the posterior lid margin, which include changes at the margin, mucocuta­ extends onto the tarsal plate. The mei­ neous junction, orifices, ducts, acini and on bomian orifices may or may not move the tarsal plate. Grading varies according to with the MCl, which will determine the features. Greater detail is given in Table whether the tear oil is delivered onto the III and is illustrated in Figures 1 and 3. surface of the tear film or not. Often, with severe disease, this question is Lid Margin redundant because the affected glands Thickening of the lid is a common feature of are non-functional. Retroplacement is meibomian gland disease, but is difficult to more common than anteroplacement. measure because of the rounded contour of (Fig. Ii). theanterior margin. It is best measured from (iii) Mucosal absorption: This may occur theposterior margin to the posterior lash line, without retroplacement of the MCl so 402 A. J. BRON ET AL.

Table IlIa. MEIBOMIAN ASSESSMENT PROFORMA

Name Hospital No. Date: EYE/R/L

Address D.O. B.

UPPER LID LOWER LID ZONE FEATURE GRADE EXTENT GRADE EXTENT

Lid margin .Thickness I-50 0--40 1-50 0--40 thin 1, thick 5 (N-3) .Rounding 011 0 0--40 Oil 0 0--40 .Vascularity: rcduced Oil 0 0--40 Oil 0 0--40 increased 0110 0--40 0110 0--40 telangiectasia 0110 0--40 0110 0--40 .Hyperkeratn 0110 0--40 0110 0--40 .Sq. blepharitis Oil 0 0-40 0110 0--40 .Trichiasis 0110 0--40 Oil 0 0--40 .Malapposition Oil 0 0-40 0110 0--40 .Irregularity 011 0 0--40 Oil 0 0--40

Mucocutaneous Junction (mciJ

Grade 1-3 span from .Anteroplaced 0-30 0--40 0-30 0--40 normal mcj to ant. .Rctroplaced" 0-30 0--40 0-30 0--40 margin in thirds .Mucosal absorp" 0-10 0--40 0-10 0-40 .Ridging 0-10 0-40 0-10 0--40

Orifices .Capping 0-10 0--40 0-10 0--40 Score lid extent .Numerical red" 0-10 0-40 0- 1 0 0--40 with no orifices .Reduplication 0-10 0--40 0-10 0--40 .Pouting 0-30 0--40 0/30 0--40 .Obliteration Narrowed 0-10 0--40 0-10 0--40 Opaque 0-10 0--40 0-10 0--40 Cuff loss 0-10 0-40 0-10 0--40 Scarrc-d 0-10 0--40 0-10 0--40 Atrophy 0-10 0--40 0-10 0--40 Grade 1* Other state

<1 mm behind mcj L I � Grade 2 --> .Retroplacement 0-30 0--40 0-30 0-4 0 �1<2 mm behind mcj .Fibre-optic sign 0110 0--40 Oil 0 0--40 pradc 3 �2 mm behind mcj

that the MCJ and orificesare still at the of the MCJ or of tissue running between the same distance from the lash line, but orifices. It may be an effect of mucosal come to lie at a new posterior lid margin. absorption when a new posterior margin is (iv) Ridging: There is a ridge-like elevation formed. (Fig. Ij). MEIBOMIAN GLAND DISEASE 403

Table IIIb I Initials: Date: EYE:RlL UPPER LID LOWER LID ZONE FEATURES GRADE EXTENT GRADE EXTENT

Main ducts

1 <1 mm exposed ---> .Exposure 0-30 0--40 0-30 0--4 D 2=",,1<2 .Cystoid diln 0-30 0--40 0-30 0--4D 3 = ",,2mm

Acini

1 = cluster visible ---> .Visibility 1-30 0--40 I-3D 0--4 D 2= yellow stripe 3 = not visible .Rudimentry OIl 0 0--40 OIl 0 0--4D .Enlarged OIl 0 0--40 OIl D 0--4n 1 = deep ---> .Concretions 0-3 D 0--40 0-30 0--4 D 2= subepithelial 3 = extruding .Chalazia OIl 0 (}--4D OIl 0 0--4 0

Secretions expressed .Inc. quantity OIl D 0--40 OIl D 0--4 D

0= normal 1 = delay 3 = blockade .Dec. quantity 0-3 D 0-4 D 0-3D 0--40 .Quality 0-30 (}-4D 0-3 D 0--40 .Foam OIl o = clear 1 = cloudy 0 0--4 D OIl 0 0--4 D 2= granular 3 = opaque solid

Tarsal plate .Hyperaemia 0-30 0--40 0-30 0--4D .Telangiectasia 0-30 0-40 0-30 0--4D .Papillae 0-30 0--40 0-30 0--4 D .Follicles 0-30 0--40 0-30 0--4 D .Cysts OIl 0 0--4 0 OIl D 0--4D .Scarring linear OIl 0 0--40 OIl D 0--4 D stellate OIl 0 0--4 D OIl 0 0--4 D .Other e.g. haemorrhage pseudomembrane membranes .Entropion 0-30 0--40 0-30 0--4 D .Ectropion 0-30 0--40 0-30 0--40

Orifices (ii) Capping: This was described by The­ (i) Number: the orifices may be redupli­ odore ('meibomiana'), and also by cated, or reduced in number, either con­ Keith. Scattered orifices may be capped genitally, sometimes as part of a by a dome of oil whose surface is tough syndrome, or as an acquired feature of but may be pierced by a needle-tip to MGD. release plentiful oil. Keith noted that the 404 A. J. BRON ET AL.

to 'light up' .32 This is most likely to be seen in the presence of pouting, or cys­ toid dilatation of the duct or gland. (Fig.4a). (vi) Obliteration: Narrowing: The punctum of the orifice may not be visible. This appearance may be associated with reduced expressibility of lipid. It is not Fig. 3. Diagram illustrating malposition of the certain if this sign can occur in the Meibomian orifices and mucocutaneous junction. a) absence of other features of oblitera­ Retroplacement of orifices b) Retroplacement of tion. orificesand mucocutaneous junction c) Retroplacement of mucocutaneous junction d) Anteroplacement of Loss of definition of the cuffs of the mucocutaneous junction. orificesis a feature which is seen with age and in early MGD. underlying orifice was ulcerated, and Vascular invasion may accompany the suggested that the cap was epithelial­ process of loss of definition. (Fig. 4b). ised.31 We hypothesise that the surface Opaque orifices: Here, the degree of lipids are oxidised and hence more sat­ opacity cf the inner cuff becomes accen­ urated, so that they solidify at lid tem­ tuated. Opaque orifices are far more perature or below to produce a surface visible at the lid margin than normal. skin. (Fig. 1k). (Fig. 10). Capping usually affects only Scarring of the region of the orifices occasional orifices and may be found in may occur, with tissue loss and depres­ otherwise normal lids. sion of the surface. It is often accom­ (iii) Pouting: An early sign of meibomian panied by a range of degenerate changes gland disease is elevation or pouting of at the lid margin. (Fig. 1p). the orifice,which is no longer flushwith It seems likely that the whole of the the surface. The meibomian orificemay above process results from subepithelial be dilated, and expression may demon­ cicatricial change which drags the pos­ strate the terminal ductule to be plugged terior lid margin towards a cicatricial with inspissated secretion or other epicentre. It is not clear whether there is material. However, such pouting orifices a true 'absorption' of lid substance in may also be blocked. At times, incipient addition to scarring, though both might exposure of the ductule (vide infra) may be envisaged to occur. give this appearance. (Fig. 11). Atrophic obliteration consists of a dis­ (iv) Retroplacement: This term is employed appearance of the orifice landmarks so to describe the result of a cicatricial pro­ that the surface epithelium may be rela­ cess involving the posterior lid margin tively smooth and the past location of and may be associated with more exten­ the orificeis marked by the tip of the dis­ sive cicatricial changes within the tarsal tal acinus seen through the marginal epi­ mucous membrane near the marginal thelium (Fig. 4c). mucosa. The orificesmay become ovally An interesting feature observed in one elongated in the plane of the ducts and atopic patient was a peri-ductular fibrosis posterior movement may be accom­ (Fig. 1q). panied by duct exposure. (Fig. 1m,n). (v) The fibre optic sign: A change in the Main Ducts light-conducting properties of the mei­ (i) Exposure: Exposure of the terminal duct bomian ducts may occur, so that illum­ of the gland in varying degrees is a com­ ination of the tarsal plate from the mon feature of MGD, suggesting the conjunctival surface with a slit-lamp presence of an irreversible cicatricial source, or through the skin with a fibre­ process in the adjacent submucosa. The optic source, causes the affected orifice duct, as it forms the orificeat the lid mar- MEIBOMIAN GLAND DISEASE 405

Fig. 43. Positive fibre optic sign. The tarsal plate is Fig. 4d. MGD: Meibomian duct exposure. Note the illuminated with a narrow slit beam; a single large venous tributaries directed anteriorly. One large Meibomian orifice lights up. tributary is draining the pretarsal space. (Arrowed).

Fig. 4b. Obliterated orifices in!"aded by new vessels Fig. 4e. Two Cigar-shaped dilations of the (arrowed). Meibomian dllcts.

Fig. 4c. Atrophic obliteration of the Meibomian Fig. 4f. A dome of clear oil, expressed at the mouth of orifices. The orifice structure is no longer seen. The lid a normal Meibomian gland (arrowed). margin is relati!"ely avascular and the Meibomian acini are seen through a/1 epithelium which is now translucent. 406 A. J. BRaN ET AL.

Fig.4g. A dome of very cloudy liquid secretion Fig. 4h. A small collection of turbid secretion expressed at the mouth of diseased Meibomian gland containing particulate matter, expressed from a (arrow head). A pouting and a capped Meibomian diseased Meibomian gland. (Arrowed). orifice is also seen.

gin, is seen to turn on its side antero­ their visibility decreases with age when posteriorly, so that it becomes visible at viewed by diffuse illumination of the tarsal the surface of the lid margin. The outer plate, or in the presence of chronic conjunc­ cuff becomes lost from view, while the tival inflammation. Observation can be inner cuff (the epithelial lining) and the improved by infrared transillumination tech­ translucent zone (the presumed dermal niques (vide supra). layer) are seen in profile. In the early Enlargement or reduction in size of the stages, the duct may be patent and func­ glands is recorded, and the presence of con­ tional; later it is not. The changes may cretions and chalazia. Gifford observed that extend over the lid margin for a number concretions might follow the line of the mei­ of millimetres, which raises the question bomian glands, and believed that they were whether it is associated with duct elonga­ deposits of lime salts within acini whose con­ tion, or absorption of the distal part of nection with the main gland was occluded.34 the tarsal plate. (Fig. 4d). The clinical features of chalazia are well (ii) Cystoid dilatation: Cystoid expansion known.}S Typically a chalazion starts as a hard may be seen anywhere along the course circumscribed painless elevation on the tarsal of the duct as a dark round or ovoid plate, visible and palpable through the skin region along the course of a meibomian which evolves slowly with time. The lesion is gland. Sometimes there are extended in line with a tarsal gland, which it replaces, cigar-shaped structures which seem to and the corresponding ductular orifice is occupy the position of one or more mei­ occluded, no oil being expressible. This lends bomian glands, but it is not easy to dis­ credence to the general view that chalazia tinguish dilatation of the duct from that arise as a result of obstruction of the gland,J6 of the gland acini by routine methods. with a secondary, granulomatous reaction of (Fig. 4e). Robin et al. were able to dis­ the acinar and peri-acinar tissues to its lipid tinguish both enlarged and distorted and constituents. also shortened glands by transillumi­ Chalazia occur more frequently under the nation biomicroscopy, using infrared upper than lower lid and more commonly in light') as used by Tapie.)2 adults than in the young. Chalazia may be single or multiple, and they may be confluent. Acini The lid may be sufficiently thickened to pre­ Visibility: As mentioned above, congenitally vent eversion. More than one lid may be absent or deficient glands will be reflected in affected. Multiple chalazia are said to be mor

secretion, but contains particulate 0,1, 2,3,4,= Nil, 0.25, 0.5,0.75, 1). matter. (Fig. 4h). The colour of these secretions varies Degree of Change from whitish-grey to yellow. (1) Some features are graded on a dichot­ (iv) Inspissated: This is a semi-solid plug, or omous scale (Oil: present or absent) e.g. of toothpaste-like consistency and may concretions,cysts, trichiasis etc. be extruded as a plug,or curled thread. (2) Other features are graded 0-3. This Expression is usually delayed or requires represents either mild, moderate or extra pressure. The material contains marked change, or the features are indi­ keratinised epithelial cells.29 vidually characterised e.g. retroplace­ Another feature which is noted,is so-called ment of the mucocutaneous junction, or meibomian foam, a frothy accumulation on duct exposure are graded according to the the lid margin or surface of the globe which number of millimetres of involvement. has been attributed to the presence of soaps in (3) Many features may show multiple grades the tear film�() althoughsupportive evidence is on the same lid margin or tarsal surface. lacking. For example, the tarsal plate may show The changes described here as part of the fine papillae in one region and cobble­ picture of meibomitis are seen in their most stones in another. In the scheme exaggerated form in the cicatricial mucous described here for degree of change, the membrane disorders in which the further most advanced feature is scored. But the changes include gross lid margin deformity, extent recorded refers to all categories of entropion and trichiasis. It does raise the the stated feature. (The extent clearly question whether these and other changes could be scored for each grade of the fea­ encountered in and described as meibomitis, ture but unless there is a specificpurpose, are due primarily to the periacinar subepi­ this is too cumbersome for routine use). thelial cicatricial disease rather than to (4) For lid thickness, which may show a quan­ primary diseases of the gland itself. However titative increase or decrease the grading is 408 A. J. BRaN FT AL.

1-5, with grade 3 representing 'normal' where length or area of abnormality are thickness, grades 1 and 2 representing scored. decreased and grades 4 and 5 represent­ ing increased thickness. In this and cer­ Discussion tain other cases, actual measurement can Many aspects of MGD and its treatment were replace grading. (e.g. of lid thickness, known to ophthalmologists one hundred and retroplacement of orifices, exposure of fifty years ago. Attempts to classify it then as the main ductules). now, combined morphological features with Some examples of grading are given below: clinical associations in such a way as to gener­ ate artificial subgroups which were not Lid Margin mutually exclusive. Rounding is graded 011; present or absent and MacKenzie was the firstto mention chronic the length of lid affected as 0-4. meibomitis as part of the condition of 'oph­ Vascularity is graded as reduced (0/1), thalmia tarsi', in which the oil glands were dis­ increased (Oil) and telangiectasia (Oil) and tended, and thickened (puriform) secretions extent affected for each feature recorded were present in i!1creased amount.41 Scarpa as 0-4. Cutaneous hyper-keratinisation, described a similar 'puriform palpebral flux'.42 squamous blepharitis, triehiasis, malapposi­ Elschnig provided a classical description of tion in primary position or upgaze, are graded meibomian gland disease and emphasised the as present or absent (011) and the extent of lid value of lid massage, at first daily and then at affected graded 0-4. longer intervals, in treatment.4'.44 Gifford described six types of disease as follows;"4 Mucocutaneous Junction Anteroplaced: Anterior movement of the Type I: Simple Hypersecretion mucocutaneous junction is scored 0-3, divid­ The expressed secretion of the glands was ing the normal width of the skin between the abnormal. being a waxy material usually in normal MC] and anterior lash line into thirds the form of semi-solid coils, but which could and grading accordingly. The highest grade be of a softer consistency. The condition was noted is scored and the extent of length of lid associated with few or no symptoms and with affected by any abnormality of this kind is the presence of a frothy scum (equivalent to scored 0-4. the current term 'meibomian foam'), at the Retroplacement of the MC] is measured with inner canthus. reference to its normal estimated location. It may move up to 1 mm posterior (grade I); it Type 2: Simple Chronic Meibomitis (Simple may lie>I mm but less than 2 mm posterior Inflammation) (grade 2), or it may lie>2 mm (grade 3). Gifford conceived this type to be similar to It will be noted, that if the mucosa of the lid type 1 and perhaps derived from it. Lid pres­ margin is absorbcd, then the MC] does not sure may express a fluid of granular com­ necessarily move back as a result. Mucosal position Cgrumous') or a whitish or yellowish, absorption or ridging are recorded as present cloudy secretion, less solid than in type 1. or absent (011) and the length of lid affected Ducts were found to be obstructed in some recorded as 0-4. glands and acini less visible because of greater opacity of the conjunctiva. Cases affected Orifices with type 2 disease showed thickening of the Reduction: The pattern of meibomian orifices lids with inflammation of the ciliary margin. is so regular that absence of orificescan read­ ily be estimated by gaps in the rows or by Type 3: Chronic Meibomitis with examination of acini when these are visible as Hypertrophy in the young. Abnormality is graded as 0/1; This was thought to be a more advanced form the length affected 0-4. (The sum of lengths of stage 2, with congested and distended over which the feature is absent is totalled for glands. Gifford described 'a strip of hyper­ this purpose, and this is a general principle trophied conjunctiva, roughened and raised MEIBOMIAN GLAND DISEASE 409

above the tarsal conjunctiva and often occlud­ (ciliary) lid inflammation (in the absence of a ing the mouths of some glands'. staphylococcal superinfection). Three further types were described on the There may be an associated meibomian basis of an association of meibomian disease seborrhoea or secondary meibomitis (vide with other affections such as chalazia, con­ infra) with dilated ductules filled with an junctivitis, and concretions. excess of meibomian secretions, and in 95% of cases there is an associated seborrhoeic Type 4: Chronic meibomitis Ivith chalazia dermatitis. The latter in their series was In this association, the lids were thickened usually mild, and variably involved scalp, and a honey-like secretion could be expressed retroauricular skin, the nasolabial folds, brow from all glands. Particular attention was given and sternum. to the occurrence of multiple chalazia, occur­ 'Staphylococcal blepharitis' was essentially ring as early as 7112 of age (e.g. around 30 a clinical diagnosis in keeping with classical chalazia) and generally presenting at an descriptions of this entity.4� There is relatively earlier age (usually under 40 years) than the more anterior ciliary inflammation than in other forms referred to above. seborrhoeic blepharitis and less greasy crusts This association between meibomian gland and scales. There is only occasionally a fol­ disease and chalazia was earlier referred to by licular or papillary conjunctivitis or punctate Addaria in 1888 (leading to difficulty in com­ keratitis (15%). Keratoconjunctivitis sicca plete lid opening in extreme cases)45 and by occurs in 50')10 of cases and it is preponderant Dianoux37 and Natanson.46 It is a generally in women (80%).47 accepted association with meibomian dys­ In their series, culture was positive for sta­ function .15 phylococcus aureus in 50%, and for staphlyo­ coccus epidermidis in the remaining 50%. Type 5: Chronic meibomitis secondary to The relative prevalence of staphylococcus chronic conjunctivitis aureus, either alone or in combination with In this situation, typifiedby the events in atro­ seborrhoeic blepharitis was thought to have phic trachoma (stage 4), there is a dense con­ decreased in recent years. Only the staphylo­ nective tissue formation overlaying and coccal group and mixed seborrhoeic/staphylo­ between the acini, which often occludes ducts coccal group showed an excess of positive leading to the formation of retention cysts. cultures for staphylococcus aureus.47

Type 6: Chronic meibomitis is associated Meibomian Seborrhoea .with tarsal concretions Meibomian hypersecretion was recognised by In case reports concretions are identified as Gifford34 although the term meibomian being irregularly disposed along the gland seborrhoea was coined by Cowper.50 It is not acini. clear that all authors used the term in an iden­ More recently McCulley et al. have pro­ tical way. McCulley et al. use the term to vided a classificationof anterior and posterior describe a condition in which an excess of blepharitis which combines a morphological secretion, contained in dilated ductules may description with an analysis of microbiolog­ be expressed in normal liquid form.47 ical findings.47 The morphological descrip­ There are limited, or no signs of inflamma­ tions, with a detailed account of meibomian tory lid disease. It is not yet established gland changes, evolved from earlier studies of whether this is a true hypersecretion, or the meibomian keratoconjunctivits by McCulley result of duct stasis and the expression of and Sciallis.4R accumulated secretions. The dilemma per­ Categories described by McCulley et al. are sists, even though some authors remark on as follows:47 (Table IV). the rapid reaccumulation of excessive secre­ Seborrhoeic Blepharitis, is a marginal tions after therapeutic expression. anterior blepharitis characterised by lid crust­ Primary meibomitis is described as an ing, and scaling which is more oily than in sta­ inflammation around the meibomian orifices phylococcal blepharitis and with less anterior diffusely affecting all the glands to a similar 410 A. J. BRON ET AL.

Table IV Forms of blepharitis

Anterior Staphylococcal Blephartis Seborrhoeic Alone with staphylococci with seborrhoea with secondary meibomitis Posterior Meibomian seborrhoea Blepharitis Primary.Meibomitis" Secondary Meibomitis* 1 Secondary to seborrheic blepharitis 2 Secondary to other disorders (e. g. atopy, cicatratrizing conjunctivitis etc) efrom McCulley et al 1982. "chalazia and concretions are regarded as complications of meibomitis degree. Solidificationof the lipid secretions is dermatitis and atopy had the most severe signs, prominent with resulting plugging of gland with secretions more difficultor impossible to orifices and build-up of secretions. Primary express and with plugs extending deeper into meibomitis is associated with bulbar injection the glands. and tarsal papillary hypertrophy in addition to In this paper we have concentrated on the superficial punctate keratitis and a reduced components which go to make up posterior break-up time.4K blepharitis in the view that the detailed The condition was found to be associated description of these changes is both scattered with a seborrhoeic dermatitis in 36% and acne in the literature and also is incomplete. It is our rosacea in 63% of cases. Patients are regarded particular interest to provide a tool to follow as having a generalised problem of their seba­ the natural history of the changes described ceous glands which also affects the meibo­ and their grouping within the major classes mian glands. summarised by McCulley et al. 45 and to study No specific pathogen is isolatable. not only their relation to anterior blepharitis Meibomitis secondary to seborrhoeic blephar­ and dermatological status but also the overlap itis is a patchy affection of the meibomian of occurrence of specific features within each glands occurring in clusters along the lid mar­ category and their evolution with time. A gin. The tissue surrounding the glands is proper understanding of such events will also inflamed, and secretions within the ductules req uire a description of the changes in lid struc­ are solidified and difficult to eli--press. Secon­ tures which occur with age and this is being dary meibomitis is associated in 100% of cases undertaken. with seborrhoeic dermatitis. The condition is References associated with symptoms of burning. L, Jester JV , Nicholaides N, Smith RE: Meibomian In both primary and secondary meibomitis gland dysfunction. I. Keratin protein expression in the frequency of staphylococcus aureus cul­ normal human and rabbit meibomian glands. Invest Ophthallllol Vis Sci 191'9a, 30: 927-35. ture is low and not in excess of that encoun­ II> Meibomius H: De Vasis palpebrarum Novis Epis­ tered in control lids. When organisms are tola p. 23. Muller, Helmstiidt. cultured from expressed meibomian secre­ , Neumann F and Elger W: The effect of a new anti· tions, they are the same as those cultured from androgenic steroid, 6-Chloro-17-Hydroxy-Icx, 2cx Methylene Pregna-'l, 6-Diene-3, 20 Dione Ace­ the lid. A further secondary category was tate (Cyproterone Acetate) on the sebaceous described including atopic,psoriatic and fun­ glands of mice . .l Inl'cst Dermato11966, 46: 561-72. gal causes of meibomian gland dysfunction 1 Strauss JS and Pochi PE: Assay of anti-androgens in (Table IV). man by the sebaceous gland response. Br.l Der· nzato11970, 82 (Suppl 60): 33-42. In an earlier study of meibomian keratocon­ , Schuster S and Thody AJ: The control and measure· junctivitis, those patients (15%) whose me i­ ment of sebum secretion . .l Invest Dermatol1974, bomitis was associated with seborrhoeic 62: 172-90. MEIBOMIAN GLAND DISEASE 411

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