The anatomical meaning of the ocular surface refers to the entire mucosal epithelium of the ocular surface, including the corneal and conjunctival epithelium, starting between the gray line of the upper and lower eyelid margins. This concept emphasizes the interdependence of the corneal epithelium and conjunctival epithelium in maintaining ocular surface health, but the acquisition and maintenance of clear visual function requires not only a healthy ocular surface epithelium, but also a stable tear film covering the ocular surface. A normal and stable tear film is the basis for maintaining the normal structure and function of the ocular surface epithelium, while the mucin component secreted by the ocular surface epithelium (both cupped and non-cupped cells) is involved in the composition of the tear film. Therefore, the ocular surface epithelium and the tear film are interdependent and affect each other. Abnormalities of either side not only affect the other side, but also lead to abnormal ocular surface function, which in turn affects visual function and causes eye discomfort. Therefore, the ocular surface in its clinical sense includes the conjunctiva, cornea, eyelids, lacrimal apparatus, and lacrimal ducts, referring to all external ocular appendages involved in the protective system that maintains the health of the ocular surface. I. The role of the eyelid in maintaining ocular surface health The active and non-random lid closure of the eyelid is very important for the protection of the eye. When an external stimulus occurs, the eyelid develops a protective lid closure reflex, which uses the optic or auditory nerve as the afferent arc and the facial nerve as the efferent arc. More importantly, the non-random transient action of the eyelid is one of the most important conditions for the formation of a stable tear film, which generally occurs every 5s-10s in normal subjects. Its role is to evenly coat the surface of the eye and to regulate the flow and evaporation rate of the surface tears accordingly, maintaining the stability of the surface tear film. The non-random transient reflex is accomplished by the ophthalmic branch of the trigeminal nerve as the afferent arc and the facial nerve as the efferent arc. Once the protective reflexes of the eyelids are impaired, the ocular surface is vulnerable to external harmful factors that can cause damage to the ocular surface and cornea. When severe chemical, thermal, or mechanical trauma causes eyelid damage, it is not only cosmetically painful, but also often results in excessive tear evaporation and impaired tear hydrodynamic distribution due to exposure of the eye and transient function, aggravating the severity of dry eye and damage to the ocular surface epithelium, leading to exposure of corneal ulcers and even corneal perforation and blindness. Therefore, eyelid reconstruction must be performed before other ocular surface reconstructive surgery and corneal transplantation. The normal ocular surface is covered with a tear film because the tear film-air interface is the first refractive surface for light to enter the eye, and maintaining a stable and healthy tear film is an important prerequisite for clear vision. The tear film can be divided from the outside to the inside into a lipid layer, an aqueous layer and a mucin layer (Figure 6-1). The precise structure of the tear film is still debated, but traditionally it is thought that the lipid layer at the surface is about 0.1 μm thick (when the lid fissure is open), the middle aqueous layer is 7 μm thick, and the innermost layer is a 20-50 nm thick mucin layer. The tear film is now thought to be approximately 40 μm thick, with no clear boundary between the aqueous layer and the mucin layer, while the majority of the tear film is composed of this mucin gel. Under normal conditions, the tear production rate is 1.2 μl/min and the refractive index is 1.336. The volume of tear fluid in the conjunctival sac is 7 μl ± 2 μl and the volume on the corneal surface is 7.0 μl. Clear protein accounts for 60% of the total protein, globulin and lysozyme for 20% each. The tear fluid also contains immunoglobulins such as IgA, IgG, IgE, etc. IgA is the most abundant and is secreted by plasma cells in the lacrimal gland. Lysozyme and r-globulin, together with other antibacterial components, form the first defense barrier of the ocular surface. Tears contain higher concentrations of K+, Na+ and Cl- than plasma. There are also small amounts of glucose (5 mg/dl) and urea (0.04 mg/dl) in tear fluid, and their concentrations change accordingly with changes in blood levels of glucose and urea. Tear pH ranges from 5.20 to 8.35, with an average of 7.35. Normally, tears are isotonic, with an osmotic pressure of 295-309 mOsm/L. (b) Tear secretion The lacrimal layer is secreted by the lacrimal gland, which has abundant innervation, mainly by cholinergic nerve fibers. In addition, there are both estrogen and androgen receptors on the lacrimal gland, and the presence of these receptors suggests that sex hormones have a role in The presence of these receptors suggests that sex hormones have a regulatory function in the secretion of the lid gland. Eyelid transients induce the release of lipids from the lid gland. It is estimated that during transients, approximately 50-70 g of gravity is applied to the eyeball, which retracts an average of 1.5 mm, and lipids are squeezed onto the corneal surface to participate in the formation of the tear film. The lipid layer reduces tear evaporation and ensures a watertight state when the lid is closed. Dysfunction of the lid gland causes tear film instability. The middle layer of the tear film is the aqueous layer, which is secreted by the primary and secondary lacrimal glands and is rich in salts and proteins. The cornea, conjunctiva and nasal mucosa are distributed with stimulatory receptors of the Vth pair of cerebral nerves, and the efferent pathway is more circuitous. The parasympathetic nerve separates from the VIIth pair of cerebral nerves at the superficial rock nerve and travels to the pterygopalatine ganglion, where the lacrimal secretory nerve fibers coexist with the zygomaticotemporal nerve, joining the lacrimal nerve (division sensory) that branches from the ophthalmic branch of the trigeminal nerve before entering the lacrimal gland, and the sympathetic efferent pathway is also contained in The sympathetic efferent pathway is also included in this. Receptors on the conjunctiva and mucosa are stimulated by external stimuli and cause reflex secretion of the lacrimal gland. The mucin layer, located at the innermost part of the tear film, contains a variety of glycoproteins and was previously thought to be produced by the cupped cells of the conjunctiva. It is now shown that both corneal and conjunctival epithelia express mucin 1 transmembrane protein, conjunctival cupped cells express MUC5AC protein, conjunctival non-cupped epithelia express MUC4 protein, MUC7 is secreted by the lacrimal gland, MUC2 and MUC5B may be secreted by conjunctival cupped cells, and MUC16 may be secreted by conjunctival epithelium and corneal complex epithelium. The mucin basal part is embedded between the microvilli of corneal and conjunctival epithelial cells, reducing the surface tension and making the hydrophobic epithelial cells hydrophilic, and the aqueous layer can evenly coat the ocular surface to maintain a moist environment. Mucins are also involved in the defense function of the corneoconjunctival epithelium against the adhesion of pathogenic microorganisms. In addition, patients with lacrimal stenosis have reduced expression of lacrimal epithelial mucins, suggesting that they may also have a role in promoting tear drainage. Insufficient mucin production, such as chemical and inflammatory disruption of ocular surface cells, can occur with inadequate corneal surface wetting and secondary epithelial damage, even if sufficient aqueous tears are produced. (C), tear film function Its main functions are: ① fill the irregular interface between epithelium to ensure the smoothness of the cornea; ② moisten and protect the corneal and conjunctival epithelium; ③ inhibit the growth of microorganisms through mechanical flushing and the antibacterial ingredients contained within; ④ provide oxygen and required nutrients for the cornea. In 1983, Thoft proposed the “XYZ theory” to maintain the dynamic equilibrium of corneal epithelium, which is a highly differentiated and rapidly self-renewing tissue. In 1983, Thoft proposed the “XYZ theory” to maintain the dynamic equilibrium of corneal epithelium, suggesting that the loss of corneal epithelium (Z) is complemented by the division of basal cells (X) and the migration of peripheral epithelium to the center (Y), which may contain corneal limbal stem cells at its base. Corneal limbal stem cells are unipotent stem cells and are found in the basal cell layer of the corneal limbus. The Vogt fence structure of the human corneal limbus is the zone where the limbal stem cells are located, and the rich vascular network near the limbus nourishes the metabolically active stem cells (Figure 6-2). However, in a pathologic setting, these vessels also transport inflammatory cells to fight infection (e.g., peripheral corneal ulcers), and inflammatory cells can release metalloproteinases leading to corneal stromal lysis. If corneal limbal stem cells are absent, epithelial wounds will not heal and persistent epithelial defects or conjunctival epithelium and neovascularization will grow into the cornea. Corneal limbal stem cells are unique structures that separate the cornea from the conjunctiva and are the power source of corneal epithelial proliferation and migration, and play an important role in maintaining the integrity of the corneal epithelium. IV. Conjunctival epithelium The conjunctival epithelium may originate from the conjunctival dome or the skin-mucosal junction of the lid margin, and some studies have suggested that stem cells of the conjunctiva are uniformly distributed across the ocular surface. It was previously thought that the cupped and non-cupped epithelia of the conjunctiva were differentiated from different conjunctival stem cells. Recent studies have shown that precursor cells of the non-cupped epithelia of the conjunctiva can induce the production of PAS-positive and AM-1-positive cells, and these positive markers are expressed only in the cupped cells, suggesting that the cupped and non-cupped epithelial cells of the conjunctiva may originate from the same stem cells. Near the lid margin, the conjunctival epithelium migrates into the keratinized, compound squamous epithelium of the eyelid skin, whereas near the corneal margin the conjunctival epithelium migrates into the corneal epithelium. The smooth conjunctiva allows the eyelid to slide over the cornea, providing protection, coating the tear film, and carrying away exogenous material. Flexible conjunctival folds and a loose conjunctival sac are significant for eye movement and maintenance of normal lid-ball relationships. In cases of conjunctival scarring (e.g. ocular aspergillosis) the normal vault structure is disrupted, leading to scarring lid entropion and impingement, causing secondary corneal damage and scarring. After trauma results in complete destruction of the cornea and corneal rim, the surrounding conjunctival epithelium moves anteriorly to cover the corneal surface. Some cells undergo morphological changes; they do not possess the pluripotency of corneal limbal stem cells, so they cannot differentiate into corneal phenotypes and do not possess the biochemical markers of mature corneal epithelium, thus causing loss of corneal transparency, which is clinically referred to as corneal phenotypic conjunctivalization.