The word blepharitis is derived from the Greek word for eyelid, and the condition is described in the Hippocratic collection (12).

Inflammation of lid became recognized as a separate clinical entity in the 19th century (13). John Dalrymple (1803-1852), surgeon at Moorfield’s Eye Hospital, gave a detailed description of blepharitis in his illustrated textbook (14).

Traditionally blepharitis was divided into two types: squamous, characterized by inflamed lid border with dry or greasy scales (squames); or ulcerative, which had small pustules of the lid follicles leading to ulceration (2).

The importance of meibomian gland dysfunction in blepharitis was recognized in a few case reports, which attributed the inflammation to either bacteria or a direct chemical effect of the secretion (15). Blepharitis in acne rosacea was also noted to be associated with meibomianitis (2).

The tarsal glands were mentioned in ancient times by Galen, but were more fully described by Heinrich Meibom in 1666 (16). Because the meibomian glands were named after Meibom (Meibomius), the correct term for their secretion is meibomium, not meibum and inflammation of the gland should be called meibomianitis not meibomitis (16).

One of the earliest descriptions of meibomian gland dysfunction, called ophthalmia tarsi, was in Mackenzie’s textbook (13). The oil glands were distended and filled with excessive amounts of thickened (puriform) secretion. Several terms were used to describe meibomian gland disease and blepharitis. These included puriform palpebral flux of Scarpa (1801), ophthalmia tarsi (13), conjunctivitis meibomianae (15), polyadenitis meibomiana chronica suppuritiva in the historical literature (17), and more recently blepharitis (2), chronic blepharo-conjunctivitis (18), meibomian keratoconjunctivitis (19), chronic meibomitis, seborrheic blepharo-kerato-conjunctivitis or seborrheic blepharitis (20).

The term meibomian seborrhea was coined by Cowper (21). Squeezing the normal tarsal plate produces a minute, clear, oily droplet at the orifice of the gland. In meibomian seborrhea, on the other hand, secretion could be abnormal in quantity and quality. Three types were described: thickened white material of cream cheese consistency, thin pus, or excess amounts of clear or mildly turbid yellowish oily
fluid. Inflammation was not a feature. Other authors use the term to describe excess normal liquid oil contained in dilated ducts (3).

Meibomian gland dysfunction is increasingly the preferred term to describe the many changes observed in the tarsal glands and orifices, some of which are related to blepharitis.

Early in the 20th century, severe staphylococcal blepharitis was an intractable condition. The treatment with penicillin ointment developed by Ida Mann in Oxford was the beginning of modern management of the condition (22). It would seem that staphylococcal blepharitis is less frequently encountered and is less severe today than in the preantibiotic era. Increasingly important is the role of meibomian gland dysfunction. Nevertheless, blepharitis in all its different forms remains a common frustrating condition for patients and practitioners, and causes a myriad of problems from irritation and dry eye because of tear film instability (19) to contact lens intolerance (23).

Until recently, the etiological theories, classification, terminology, and management of blepharitis still owed more to historical dictum than rational science.

The normal adult lid margin, measured from the posterior lash line to the sharply curved posterior lid border, is 1.95 (±0.07) mm wide in the upper lid and 1.87 (±0.06) mm in the lower lid (24). The posterior quarter is lined with mucous membrane and ends with an abrupt right angle edge (Fig. 30-1A). This allows smooth contact with the globe, similar to a windscreen wiper, and change in conformation by rounding leads to ocular surface dysfunction. Increased rounding occurs in the upper lid with age and in the lower lid as a consequence of posterior blepharitis (24).

The anterior three quarters of the lid margin is composed of skin and the front edge is more rounded than the posterior lid margin. In young people, the lid margins are relatively avascular, although the papillary architecture of the mucosal vessels is easily identified. Cutaneous vessels become more obvious with age. A segmental venous drainage between the meibomian orifices has tributaries from the mucosa, which pass forward in the dermis (Fig. 30-1B) (7).

The mucocutaneous junction forms a curved line along the full length of the lid, parallel to its posterior edge. The lashes emerge in the anterior half of the skin-lined portion and the meibomian gland orifices are located just in front of the mucocutaneous junction in the cutaneous part (7).

The meibomian glands are modified, elongated sebaceous glands in the tarsal plates of the lids that open onto the lid margin. The main structure is the duct extending the full length of the gland. About 30 to 40 vertically orientated glands are found in the upper lid and slightly fewer in the lower lid. The concentration of these enlarged glands in the small area of the lids implies an important demand for lipid secretion to maintain a healthy ocular surface. They are tubular-acinar glands, composed of grapelike clusters of single or composite acinar lobules opening into lateral ductules on either side of the main duct. The duct is lined with partially keratinized epithelium (25). It terminates in an orifice flush with the surface of the lid margin. These orifices are visible with slit-lamp examination, which reveals a series of concentric zones, most easily identified in youth (Fig. 30-1A). There is a central punctum surrounded by an opaque cuff, presumably the keratinized lining of the duct. Around this is a translucent dark annulus of dermis. In nonpigmented skin, an outer cream colored, subepithelial cuff is seen that probably represents a deep structure such as the distal tip of the acinus or the muscle of Riolan, fine muscular extensions of the pars marginalis of orbicularis oculi (7,26).

The secretion of the meibomian glands is holocrine, derived from lysis of the secretory cells. The acini are lined with glandular epithelium, cuboidal and fat-free peripherally and fat-laden centrally. The cells break down when mature and release their contents into the ductules. The main duct is filled with fat and can be seen as a yellow streak through the conjunctiva. Gentle pressure expresses a small dome of clear oily fluid over the gland orifices in normal individuals.

The composition of meibomian lipid is distinct from sebum, reflecting its different functions. Meibomian oil remains liquid at lid temperature (16). The melting point is a range with some components remaining semisolid until complete melting occurs.

The study of meibomian lipid chemistry is complex and affected by sampling and methods of analysis. Rancification of oils during preparation and problems with analysis of pooled samples should be considered in interpreting the results from the older literature (16). Indeed significant individual variation in the components of meibomian secretion exists in the normal population.

Wax, from the Anglo-Saxon word weax, meaning beeswax, is an important component of the surface covering of animals and plants. Waxes contain esters of long-chain fatty acids with long-chain fatty alcohols, usually of a similar length. In general, about 84% of meibomian lipid is composed of nonpolar lipid wax esters and sterol esters. The esters contain straight-chain, branched-chain, unsaturated, and hydroxy fatty acids with chain lengths of C₁₂ to C₃₄ (16,27). Smaller amounts of diesters, triesters, free sterols, triglycerides, and free fatty acids are also present (28). Triglycerides compose 6% of the total, and only 0.5% to 1% is free fatty acids (29).

The wax esters are composed of relatively short chain lengths (18 carbons or less). The major peak is a C₄₂ ester containing 16:1 fatty acid and iso-C₂₆ alcohol (30).

The major esterified sterol is cholesterol, but smaller amounts of others, including lathosterol, have been identified (30). The sterol esters use longer chains (20 carbons or more) than the wax esters (28).

Unsaturated fatty acids (containing a C=C double bond) in esters are particularly important because of their lower melting point compared to equivalent saturated fatty acids. Differences in the fatty acids esterified to waxes and sterols are found between patients with blepharitis and normal controls (31). Paste-like meibomian secretion obtained from blepharitis patients contains relatively low amounts of the 18-carbon unsaturated oleic acid (cis-9-octadecanoic acid) compared to more liquid meibomian lipid samples (32).

There are many types of lipid molecules in meibomian secretion. The combination of a variety of fatty acids with several fatty alcohols and sterols can generate an enormous number of different wax ester and sterol ester molecules (28,31).

Pure lipids are hydrophobic, and do not spread on the aqueous tear film. A surfactant of polar lipids is required, the hydrophilic end in the aqueous and a hydrophobic tail supporting the overlying lipid layer. The low amounts of polar lipids present in meibomian secretion, including phospholipids, sphingolipids, ceramides (fatty acids linked by an amide bond to the amine group of a long chain sphingoid base), cerebrosides, and polar unbranched saturated fatty acids, therefore, have an important functional role. It is likely that they form an extremely thin layer, one to three molecules thick, which acts as a surfactant between aqueous tears and the thicker nonpolar lipid layer (33). Low levels of two polar phospholipids, phosphatidylethanolamine (cephalin) and sphingolipid, are associated with keratoconjunctivitis sicca in patients with blepharitis, presumably due to increased tear evaporation (34).

The combination of all these molecular species gives the semisolid lipid mixture properties that allow its various functions. It must have the correct viscosity to flow out of the gland orifice and the correct range of melting points. The oily waxy meibomian substance is secreted onto the edge of the eyelid. Some of the secretion spreads onto the tear film forming the superficial lipid layer. The lipid layer component must have spreading characteristics that ensure coverage of the preocular tear film between blinks. This layer retards evaporation of tears and provides the optical qualities necessary for good image formation by the eye (35).

The remaining lipid on the lid forms a hydrophobic wall, preventing overspill of tears onto the skin, hindering contamination of the preocular tear film lipids with sebaceous lipids and ensuring a tight seal when the eyelids are closed.

Changes in the lipid secretion either endogenously or after modification by lipase enzymes derived from bacteria, can alter the properties of the oil. This can cause increased viscosity leading to stagnation in the glands, changes in rheology affecting tear film stability, and release of free fatty acids and other molecular species, which can directly cause irritation of the eye.