Rosacea of the skin is characterized clinically by erythema, telangiectases, papules, and pustules, which are located mostly on the face. Often lesions appear in the middle of the face and are accompanied by telangiectases. On sites other than the midface like forehead, perioral, and periocular regions, however, erythematous papules and papulopustules may be unaccompanied by telangiectases. In contrast to acne, patients with rosacea have no comedones. Histopathologically the papules and pustules are characterized by peri-infundibular, and intra-infundibular infiltrates that, at the outset of the disease, contain lymphocytes joined by spongiosis of infundibula, [38,39] followed by neutrophils forming intra-infundibular pustules. Only later, plasma cells and histiocytes appear, the latter often forming granulomas as a consequence of rupture of infundibula and as a "foreign body response" to contents of infundibula spilled into the dermis. In short, the infundibula seem to play a key role in rosacea. Consequently, analogous structures should be the focus of interest in order to understand the situation of rosacea affecting the eye. To what extent sebaceous glands are involved in the pathogenesis of rosacea is not known. Rarely, however, are infiltrates of inflammatory cells seen in sebaceous lobular epithelium in lesions of rosacea, making it unlikely that they are quintessential pathogenetically. Moreover, rosacea also appears at times in prepubescent children in whom sebaceous glands are not yet developed, only immature mantles being found around follicles.

The skin of the eyelid is basically identical to the skin of the rest of the face (Fig. 1). At the lid margin, the keratinized epidermis blends with a mucous membrane, the conjunctiva. Between the epithelial layers of the eyelid a connective tissue is situated that contains muscle, collagen fibers, glands, and follicles. At the free margin of the lid the hair follicles of the eyelashes are positioned; these follicles are identical to those elsewhere in the skin but they lack the arrector pili muscle. The sebaceous glands around these follicles are called the Zeiss glands and, just as in any other hair follicle, these sebaceous glands enter at the junction of the infundibulum and the isthmus. The musculus orbicularis oculi, a skeletal muscle, is situated in the subcutaneous tissue of the eyelid in front of the tarsus, a fibrous plate that gives form and stability to the eyelid. Between the tarsus and the conjunctiva the meibomian glands, which are also called the tarsal glands of the eyelid, are located. They are disposed in a plane vertically oriented to the lid margin, the glandular alveoli being connected by short lateral ducts to a long excretory duct with a stratified squamous epithelium. The ducts of those glands open to the inner free margin of the lid at the junction of skin and conjunctiva through channels that show infundibular differentiation marked by keratohyalin granules. While conventionally the meibomian glands are considered to be unassociated with hair follicles, they must derive from a infundibulo-folliculo-apocrine-sebaceous germ just as any other sebaceous gland because in one pathologic condition, so-called distichiasis, small hairs grow out of every opening of a meibomian gland. In a healthy condition, however, the follicle as well as apocrine gland do not develop while sebaceous glands and infundibula form fully.

The precorneal tear film (Fig. 2) consists of three layers that are produced by different glands. The outermost lipid layer measures approximately 100 mm in thickness. It is produced by the meibomian glands and consists of cholesterol, cholesterol esters, triglycerides, and phospholipids. The meibomian glands are sebaceous glands and, just as all sebaceous glands, they produce a lipophilic secretion very similar to sebum. The intermediate layer consists of a watery fluid containing electrolytes, glucose, and proteins manufactured by the lacrimal gland. The lacrimal gland is an exocrine gland located in the upper lateral orbita, which manufactures the tear fluid. The innermost mucoid layer has a thickness of 30 to 40m and is produced by the accessory glands positioned in the eyelid as well as by the goblet cells of the conjunctiva. Approximately 1.5 ml of tear fluid are produced per minute and are distributed on the cornea by the eyelid movement. Approximately 10 to 15% of the tear film is exchanged per minute. The tear fluid is drained through the tear-nose channel. The secretion of Zeiss glands, the sebaceous glands associated with the eyelash follicles, also contributes to the stability of the tear film as their fatty sebaceous secretion envelops the eyelashes, which hold the tear film on the cornea.

The tear film has a thickness of approximately 7–9 mm and an evaporation rate of 0.06 ml/cm2 per minute. It contributes to the nutrition of the cornea which is devoid of blood vessels and nourished only by way of diffusion. It also is essential to the optical function of the eye.

A pathologic condition of the eye manifests itself as a so-called "dry eye," a "sicca syndrome." In that circumstance, the tear film breaks. Consequently, the cornea is malnourished and becomes more susceptible to irritation and infection. Multiple causes may lead to such a state of a dry eye, e.g., the production of tears by the lacrimal gland may be reduced such as it is the case in Sjögren syndrome, or tears cannot be held by the eyelid because of an ectropium. As a consequence of both of these conditions, patients may experience similar complications such as conjunctivitis and keratitis.

The sicca syndrome can be measured by way of the Schirmer test. The stability of the tear film can be investigated with fluorescent colors and slit lamp examination of the eye.

The cornea is an avascular tissue with very few cells but prominent innervation (Fig. 3). The nutrition of the cornea is by way of diffusion from the precorneal tear film, the chamber fluid, and the vascularization at the margin. The cornea consists of several layers, from outside to inside: epithelium, Bowman membrane, stroma, Descemet membrane, and endothelium.

Blepharitis: Inflammation of the eyelid. The term is not specific as various types of inflammatory processes can cause inflammation of the eyelid among them being conditions as diverse as rosacea, allergic contact dermatitis, cicatricial pemphigoid, and herpetic infection. In regard to rosacea, blepharitis is often used as a synonym to Meibomitis (see below).

Meibomitis: Inflammation of the meibomian gland. Strictly, this diagnosis should only be made by way of histopathology when infiltrates of inflammatory cells are found within the sebaceous lobules of the meibomian gland in the eyelid. Rarely, however, are histopathologic studies undertaken of the eyelid. Mostly the term Meibomitis is used as a clinical term when inflammation is seen at the lid margin centered around the openings of the meibomian glands. Some authors observed also plugging of meibomian ducts with corneocytes and suggested that squamous metaplasia may be a sign of Meibomitis.

Meibomian (gland) dysfunction: Not clearly defined. This term has been used to designate pathologic conditions of the meibomian glands and/or ducts which are typified by a decreased secretion. In such conditions, the outermost lipid layer of the tear film is reduced and the tear film breaks, which is one of the reasons for a "dry eye," the so-called sicca syndrome (see below).

"Sicca syndrome": A reduced tear film. Strictly speaking, the "sicca syndrome" is not a syndrome but a clinical finding. The reduction of the tear film can be measured by the Schirmer test and patients complain about dry eyes. The reasons for a reduction in the tear film are many and may affect any of the layers of the tear film. The most well known reason is reduced secretion of the lacrimal gland in Sjögren syndrome, but impaired secretion of meibomian glands also causes the same clinical finding of a dry eye because the watery layer of the tear film evaporates more easily when not sufficiently protected by an outermost lipid layer manufactured by meibomian glands.

Keratitis: This term means strictly speaking "inflammation of the cornea," but inflammation requires vascularization and infiltrates of inflammatory cells. An avascular tissue such as the cornea cannot develop true inflammation but only infiltrates of inflammatory cells. Moreover, the diagnosis of keratitis is usually a clinical diagnosis and not a histopathologic diagnosis. What is referred to as "keratitis" consists of defects in the cornea. Defects can be superficial, affecting only the outermost epithelium, or be deep and even, penetrating the cornea. When ulceration develops, it is usually followed by infiltrates of inflammatory cells. Fluorescent colors can be used to demonstrate ulceration of the cornea in a split lamp examination of the eye. The reasons leading to ulceration of the cornea are far reaching from traumatic to infectious. One reason for ulceration of the cornea is malnutrition when the tear film is not intact. Such defects of the cornea are the common end pathway of any disease associated with a reduced tear film (see above). Keratitis is almost always accompanied by conjunctivitis, i.e., dilation of vessels and inflammatory infiltrates in the conjunctiva.

It is likely that the same pathologic process that causes rosacea on the face is also responsible for rosacea on the eye (Figs. 3–5). The corresponding structure between the eye and the skin of the face is the eyelid. Essentially, the eyelid is nothing else but skin with a few anatomic alterations. On the face, the most consistent finding in lesions of rosacea is inflammation in and around the infundibula. On the eyelid, infundibula exist at the hair follicles of the eyelashes, the Zeiss glands, but also meibomian glands enter to the eyelid margin through channels that are identical in differentiation to infundibula. These channels have a squamous epithelium just as the infundibula, a finding that by some authors has been misinterpreted as "squamous metaplasia." Infiltrates in and around these epithelial funnels are responsible for the key feature of "ocular rosacea," namely, blepharitis. In rosacea, blepharitis starts typically at the ostia of eyelashes and meibomian glands. Sometimes, even pustulation can be seen at the eyelid margin.

But how can involvement of the cornea in rosacea be explained when infundibula are completely absent there? What is the connection between "blepharitis" on one hand and "keratitis" on the other? The answer resides in the observation that patients with rosacea often have a pathologic Schirmer test, a so-called dry eye. A dry eye develops consequent to an imbalance of the tear film. Since the lacrimal gland is entirely uninvolved in the process of rosacea, the role that Zeiss and Moll glands play in the stability of the tear film is crucial to the understanding of the process. When infundibula of eyelashes and infundibular channels of meibomian glands are affected by the process of rosacea, the secretion of those glands may be impaired causing a thinning of the outermost lipid layer of the tear film. If that layer is diminished, the watery layer of the tear film is more likely to evaporate. What follows is a common end pathway to any diseases that causes a reduced tear film, from Sjögren syndrome over ectropium to rosacea. If the tear film is broken for a longer period of time, defects will develop in the cornea because the nutrition of the cornea is impaired. Such a keratitis sicca is always accompanied by conjunctivitis and is usually referred to as "keratoconjunctivitis sicca."