Ординатура / Офтальмология / Английские материалы / Ocular Periphery and Disorders_Dartt, Bex, Amore_2011

Glossary

Dacryocystitis – An infection of the efferent tear ducts. Dacryolithiasis – The formation and presence of dacryoliths.

Dacryostenosis – The obstruction or narrowing of one or both canaliculi or the nasolacrimal duct. It may be present at birth.

Epiphora – An abnormal overflow of tears down the face.

Horner’s muscle – A branch of the orbicularis oculi muscle passing behind the lacrimal sac;

it contributes to the lacrimal pump.

Natural killer (NK) cells – A type of cytotoxic lymphocytes that constitute a major component of the innate immune system.

Pseudostratified epithelium – A type of epithelium that, though comprising only a single layer of cells, has its cell nuclei positioned in a manner suggestive of stratified epithelia.

Rheology – The study of the flow of matter: mainly liquids but also soft solids or solids under conditions in which they flow rather than deform elastically. It applies to substances which have a complex structure, including muds, sludges, suspensions, polymers, many foods, bodily fluids, and other biological materials. The flows of these substances cannot be characterized by a single value of viscosity (at a fixed temperature) – instead the viscosity changes due to other factors.

The upper and lower canaliculi, lacrimal sac, and nasolacrimal duct are subsumed under the terms nasolacrimal ducts, efferent tear ducts, or lacrimal passages. After birth, the function of the nasolacrimal ducts is to drain tear fluid into the inferior meatus of the nose.

The physiology of lacrimal drainage has been under study for over a century. Various mechanisms have been proposed to explain tear drainage, reflecting the unique anatomic configuration of the efferent tear ducts (Table 1). These include an active lacrimal pump mechanism that functions by contraction of the orbicularis eye muscle; a wringing-out mechanism governed by a system of helically arranged fibrillar structures; the bulging and subsiding of a cavernous body that surrounds the lacrimal sac and nasolacrimal duct; the action of epithelial secretion products; and physical factors such as capillarity, gravity, respiration,

evaporation, and absorption of tear fluid through the lining epithelium of the efferent tear ducts. Nevertheless, the complex mechanism by which the tear fluid is brought from the ocular surface to the inferior meatus of the nose is yet not completely understood.

The median transit time of a single applied teardrop containing fluorescein dye has been shown to be 4.5 min or 8 min, depending on whether the fluorescein is applied without or with anaesthetizing the ocular surface, respectively. Without anaesthetizing, some reflex tearing of the lacrimal gland is initiated that increases lacrimal fluid volume, which in turn shortens the dye transit time. However, the passage time is subject to distinctive intraindividual variability with a standard deviation of 3.23 min and minimum and maximum values between 15 s and more than 18 min, respectively. There may be several factors that determine the high level of intraindividual variability in dye transit time: fluctuations within a single individual over time, family predisposition, emotional status, the fluid balance, basal tear film production, atmospheric conditions of testing, tear pump efficiency, hormonal status, and blink rate.

History

The first exact description of the efferent tear duct system dates back to Giovanni Battista Carcano Leone (1574). Together with the work of Niels Stensen (1662) on tear secretions, Leone’s explanations led to a plausible concept for the entire lacrimal system.

Development

During the third month of embryological development, the eyelid folds contact each other and fuse. The specialized structures of the eyelids develop during the period of fusion. Some epithelial cores from both margins of the lid folds get buried in them, at the inner sixth of the eyelids, to form the precursors of the puncta and canaliculi. The epithelial buds, which have grown inside the tarsus, become canalized, as do the epithelial cores that will form the puncta and canaliculi. In the sixth month, the nasolacrimal system becomes patent as a result of lysis in the central cells of both epithelial rods (one starting from the inner canthus and extending toward the nose and the other starting from the nasal mucosa and extending

Table 1 Mechanisms of tear drainage

Active lacrimal pump mechanism aided by contraction of the lacrimal portion of the orbicularis muscle

Distension of the lacrimal sac by the action of the lacrimal portion of the orbicularis muscle

Epithelial secretion products (mucins, TFF peptides, and surfactant proteins) of the epithelia of the lacrimal sac and nasolacrimal duct

Wringing-out mechanism governed by a system of helically arranged fibrillar structures

Opening and closing of the lumen of the lacrimal passage effected by the bulging and subsiding of the cavernous body

Capillarity

Respiration

Evaporation

Absorption of tear fluid through the lining epithelia of the lacrimal sac and nasolacrimal duct

toward the inner canthus) at their site of junction. At birth, the nasolacrimal canal is patent from the puncta to the nasal mucosa, under the lower concha (also known as turbinate). The lower end of the lacrimal duct is separated from the inferior meatus of the nasal cavity by a membrane (Hasner’s membrane) consisting of the apposed mucosa lining the nasal fossa and the lower end of the duct. Many newborns suffer from congenital obstruction of the lacrimal pathways. The rate of congenital membranous stenosis of the lacrimal excretory systems in newborns has been reported to be as high as 50%. Fortunately, there is a high rate of spontaneous relief of the epiphora within the first 9 months of life. The repair of a lacrimal duct obstruction should therefore only rarely be performed prior to this age.

Anatomy and Dimensions

The lacrimal passages consist of a bony passage and a membranous lacrimal passage. The bony passage is formed anteriorly by the frontal process of the maxilla and posteriorly by the lacrimal bone. The membranous part includes the lacrimal canaliculi, the lacrimal sac, and the nasolacrimal duct (Figure 1).

Each canaliculus starts with a 0.25 mm (upper) to 0.3 mm (lower) large, round, oval, or slit-like lacrimal punctum with a nearly 2-mm-long vertical part. Consequently, the lacrimal canaliculus nearly runs at a right angle into the horizontal part, which measures approximately 8 mm. In most cases (c. 65–70%), the two canaliculi join to form a common canal that penetrates the wall of the lacrimal sac regularly 2–3 mm below the apex of the sac, termed fornix or fundus sacci lacrimalis. The vertical diameter of the sac is close to 12 mm, the saggital 5–6 mm, and the transversal 4–5 mm. The nasolacrimal duct normally measures 12.4 mm in adults. The bony coat is nearly 10 mm long and has a diameter of 4.6 mm.

The upper and lower canaliculi are lined by pseudostratified/stratified columnar epithelium and surrounded by a dense ring of connective tissue as well as muscle fibers of the lacrimal portion of Horner’s muscle (orbicularis oculi muscle and tensor tarsi muscle). The lacrimal sac and the nasolacrimal duct are lined with a double-layered epithelium, revealing a superficial columnar layer with microvilli and a deep flattened layer of basal cells. Both layers sometimes appear pseudostratified. Some cells of the nasolacrimal duct are lined by kinocilia (sincular kinocilium; a motile cilium on the apex of distinct cells, for example, cells covering the nasal cavity and nasal sinus). Besides epithelial cells, goblet cells are also integrated in the epithelium, sometimes forming intraepithelial mucous glands. Moreover, small seromucous glands are present in the lamina propria, especially in the fundus of the lacrimal sac.

Comparative Anatomy

Unlike the human and ape nasolacrimal systems composed of upper and lower canaliculi, the lacrimal sac, and the nasolacrimal duct, the lacrimal systems in dogs, rabbits, cats, deer, pigs, and rats consist solely of the upper and lower canaliculi, leading directly into the nasolacrimal duct. Human, ape, dog, rabbit, cat, deer, and pig tissues reveal a pseudostratified, columnar epithelium with double layering in most areas, a basal cell layer and a superficial columnar layer. The rat shows a multilayered epithelium. The upper cell layers consist of larger squamous elements over several layers of essentially cuboidal cells. Goblet cells are integrated in the epithelia of humans, rats, and cats as solitary cells and in human and rat epithelia as intraepithelial mucous glands. By contrast, the epithelia of apes, dogs, rabbits, deer, and pigs contain no goblet cells. However, ape, dog, rabbit, and pig epithelia do contain many epithelial cells that show mildly positive staining with alcian blue (pH 1.0) in the upper cytoplasm; from investigations in dogs, it is known that this positive staining corresponds to mucins (authors’ observations). The cells with the mild staining are mostly arranged in cell groups. There are also epithelial areas without such cells or cell groups. Subepithelially, the lamina propria of the human lacrimal passage is composed of loose connective tissue containing elastic fibers and lymphatic cells and a rich venous plexus comparable to a cavernous body. A surrounding cavernous system of blood vessels is also found in apes, dogs, rabbits, deer, and pigs, but is absent in rats and cats. Small seromucous glands with excretory ducts opening into the lacrimal passage are integrated in the lamina propria of humans and pigs. None of the other animals possesses seromucous glands. Compared to humans, the efferent tear duct system of dogs and pigs is long. Therefore, the similarities between rabbit and human nasolacrimal ducts support the

use of the rabbit for experimental studies of the efferent tear duct system.

Tear Transport through Canaliculi

The drainage of tears involves a number of different mechanisms that are not completely understood. It has been suggested that physical factors such as gravity, respiration, and evaporation might play a role in the drainage of tears through the lacrimal passage. Brienen and Snell postulated that the main, and presumably the sole, force that impels lacrimal flow from the conjunctival sac is the pressure brought about by closing of the eyes; in all probability, their expansions and contractions are secondary consequences of pressure fluctuations in the conjunctival sac. Jones introduced the concept of the lacrimal pump system which functions with blinking and might be responsible for lacrimal drainage by analyzing the structure of the medial palpebral ligament and the palpebral part of the orbicularis oculi muscle. It has also been shown that, during blinking movements, the canaliculi and medial canthal tendon are compressed and a uniform volume of lacrimal fluid is squirted into the lacrimal sac. The expansion of the lacrimal sac then causes suction

during the opening phase of the blink, and, after the opening phase of the punctual areas, the canaliculi and lacrimal sac vacuum breaks to reload with tear fluid. The small canaliculi may also act as capillary tubes. Lacrimal fluid is attracted by capillarity into the lacrimal puncta, and, upon closing of the eyelids, the contraction of the preseptal muscle creates a negative pressure and sucks the tear fluid into the sac. The existence of negative pressure and the active transport of tears into the sac are, however, questioned by many. Nevertheless, the importance of Horner’s muscle becomes clear in cases of facial palsy. Tears are not pumped through the lacrimal system. Even with a Jones tube (a small tube allowing tears to drain into the nose) in place, there will be a decrease in tear flow if the orbicularis muscle function is insufficient. Support for the existence of a canalicular pump system on lid closure also came from experimental work carried out by others. Amrith et al. demonstrated that the puncta elevate and meet forcefully when the lids are half shut, and, on complete lid closure, the canaliculi and sac are compressed, forcing tears into the sac and nasolacrimal duct. The elastic expansion of the channels during lid opening and the drawing apart of the puncta break the vacuum, and the tear from the marginal strip is drawn into the puncta. Doane concluded that the force generated in the canaliculi

during lid closure alone is sufficient to transport the nonreflex secretion, as it is less than 1 ml min 1. If excess fluid is available, as in reflex tearing, it is possible that the sac may contribute to drawing the fluid. However, high-speed photographic and cinematographic techniques have not been useful in demonstrating what happens in the lacrimal sac during a blink. Even the role of gravity is not clear since Hurwitz concluded that gravity does play a significant role in the transport of tears.

Tear Transport through Lacrimal Sac and Nasolacrimal Duct

It is a popular misinterpretation that the tear fluid is drained into the inferior meatus of the nose by the contraction of musculature surrounding the lacrimal sac and/or nasolacrimal duct. Underneath the epithelium, the lamina propriae of the lacrimal sac and nasolacrimal duct consist of loose connective tissue containing a thin layer of elastic fibers and a rich venous plexus situated under this tissue that is connected caudally to the cavernous body of the nasal inferior turbinate. Collagen bundles as well as elastic and reticular fibers between the blood vessels of a rich venous plexus are arranged in a helical pattern and run spirally from the fornix of the lacrimal sac to the outlet of the nasolacrimal duct, where they contribute biomechanically to tear outflow during blinking. Specialized types of blood vessels are distinguishable inside the vascular tissue and are comparable to a cavernous body.

The blood vessels are specialized arteries (barrier arteries), venous lacunae (capacitance veins), veins (throttle veins), and arteriovenous anastomoses. They facilitate the opening and closure of the lumen of the lacrimal passage by swelling and shrinkage of the cavernous body. Swelling occurs when the barrier arteries (arteries with an additional muscular layer) are opened and the throttle veins (veins whose tunica media contains a muscle layer of helically arranged smooth muscle cells) are closed. Filling of the capacitance veins (widely convoluted venous

lacunae) occurs at the same time as closure of the lumen of the lacrimal passage. By contrast, closure of the barrier arteries and opening of the throttle veins reduce the blood flow to the capacitance veins, simultaneously allowing blood outflow from these veins with resultant shrinkage of the cavernous body and dilatation of the lumen of the lacrimal passage. Arteriovenous anastomoses enable direct blood flow between arteries and venous lacunae; thus, the subepithelially located capillary network can be avoided and rapid filling of capacitance veins is possible when the shunts of the arteriovenous anastomoses are open. While regulating the blood flow, the specialized blood vessels permit opening and closing of the lumen of the lacrimal passage, effected by the bulging and subsiding of the cavernous body, and simultaneously regulate tear outflow.

The presence of the cavernous body is lacking in nearly all textbooks of anatomy and is therefore unknown to most nasolacrimal surgeons and radiologists. It is, however, densely innervated. Epiphora related to emotions such as sorrow or happiness occurs not only by increased tear secretion from the lacrimal gland and accessory lacrimal glands, but also by closure of the lacrimal passage. This mechanism acts, for example, to provide protection against foreign bodies that have entered the conjunctival sac: Not only is tear fluid production increased, but tear outflow is also interrupted by the swelling of the cavernous body to flush out the foreign body and protect the efferent tear ducts themselves. Moreover, it can be assumed that the valves in the lacrimal sac and nasolacrimal duct described in the past by Rosenmu¨ller, Hanske, Aubaret, Be´raud, Krause, and Taillefer could be caused by different swelling states of the cavernous body and must therefore be considered speculative.

In fact, the cavernous body of the efferent tear ducts plays an important role in the physiology of tear outflow regulation and can be influenced pharmacologically. Interestingly, administration of a decongestant drug or insertion of a foreign body at the ocular surface prolong the tear transit time significantly, but by different mechanisms (Figure 2). The application of a

decongestant drug simultaneously with insertion of a foreign body shortens the tear transit time significantly compared to the effect of the decongestant drug alone, but there is no significant difference compared with application of a foreign body alone. The tear transit time is independent of side (right or left), gender, whether eyeglasses are worn, and whether the person is suffering from a common cold.

Tear outflow is further supported by the regional distribution of epithelial secretion products in the lacrimal sac and nasolacrimal duct (see the section titled ‘Innate immune mechanisms’). These include membranebound and secretory mucins and trefoil factor family (TFF) peptides and, as recently shown, surfactant proteins. The epithelial secretion products might influence the rheology and flow of tears through the efferent tear passages. There is speculation that at the ocular surface, mucin composition, distribution, and function are influenced by shear forces generated during blinking. Such forces are absent in the nasolacrimal ducts, and other mechanisms are necessary to ease the flow of tears. From the data available so far, it can only be said that mucins, TFF peptides, and surfactant proteins are likely to interact and may thus affect tear outflow. However, concrete data addressing this feature are lacking.

Innate Immune Mechanisms

As is the case with all mucosae, the surfaces of the lacrimal sac and the nasolacrimal duct are in constant interaction with environmental microorganisms and are therefore vulnerable to infection. Similar to conjunctiva and cornea, the mucosa of the nasolacrimal ducts has developed a number of different nonspecific defense systems that can protect against dacryocystitis (Table 2); the epithelial cells thus produce a spectrum of different antimicrobial substances, such as lysozyme, lactoferrin, and secretory phospholipase A2, as well as defensins, which protect against the physiological germ flora inside the lacrimal passage. When infectious and/or inflammatory

Table 2 Functions of the epithelia of the lacrimal sac and nasolacrimal duct

Secretion of antimicrobial substances (lysozyme, lactoferrin, secretory phospholipase A2, bactericidal-permeability- increasing protein, heparin-binding protein, human b-defensins, and surfactant proteins A and D)

Secretion of mucins (MUC2, MUC5AC, MUC5B, MUC7, MUC8) and production of membrane-bound mucins (MUC1, MUC4, and MUC16)

Secretion of trefoil factor (TF) peptides (TFF1 and TFF3) Secretion of surface active components (surfactant proteins

B and C) Production of lipids

Absorption of tear fluid components

dacryocystitis pose a threat, changes in the expression pattern occur, inducing the production of some of the antimicrobial substances, for example, antimicrobial peptides such as human inducible beta defensins 2 and 3, which are not produced under healthy conditions in the efferent tear ducts.

Besides supporting tear outflow, the product of the mucus component formed by goblet cells and epithelial cells has been attributed largely to immunological response. It contains mucins MUC1, MUC2, MUC4, MUC5AC, MUC5B, MUC7, MUC8, and MUC16 and probably additional mucins. Moreover, the epithelium of the nasolacrimal ducts expresses and produces – as already mentioned

– the TFF peptides TFF1 and TFF3. Disturbances in the balance of single mucins or TFF peptides are important in the development of dacryostenosis, daryolithiasis, and daryocystitis. Mucins have several functions. In addition to lubricating the mucosa and waterproofing to regulate epithelial cell hydration, mucins protect mucosal surfaces against potentially harmful substances; however, a variety of oral and intestinal bacteria have been shown to produce sialidase, an enzyme that can degrade mucins by removing sialic acid. Additionally, oral and intestinal bacteria synthesize an array of other glycosidases that can attack the oligosaccharide residues of mucins. Early results of current investigations reveal that such glycosidases are also present at the ocular surface.

Finally, secretory immunoglobulin A (sIgA; the class of antibodies produced predominantly against ingested antigens, found in body secretions such as saliva, sweat, and tears, and functioning to prevent the attachment of viruses and bacteria to epithelial surfaces) is incorporated into the mucus layer of mucosal surfaces, supplementing the protective activity. It can interact with functionally diverse cells, including epithelial cells, B- and T-lymphocytes, natural killer (NK) cells, cells of the monocyte/macrophage lineage, and neutrophils. All of these latter cell types, as well as sIgA, are present on and in the nasolacrimal ducts and belong to the lacrimal mucosal immune system (see below). This defense is supported by the collectins (surfactant-asso- ciated proteins) SP-A and SP-D in the service of nonspecific natural immune defense and in the activation of the adaptive immune system. As a substance intrinsic to drained tear fluid, they protect the ocular surface in conjunction with IgA, defensins, and mucins against infection by Pseudomona aeruginosa, Staphylococcus aureus, and other pathogenic microbes in preventing the formation of dacryocystitis.

Adaptive Immune Mechanisms

Subepithelially, lymphocytes and other defense cells are amply present inside the efferent tear ducts, sometimes

aggregated into follicles. Aggregated follicles are present in nearly a third of nasolacrimal ducts from unselected cadavers with no known history of disease involving the eye, efferent tear ducts, or the nose. These aggregations and the surrounding tissue fulfill the criteria for designation as mucosa-associated lymphoid tissue (MALT). They consist of organized mucosal lymphoid tissue characterized by the presence of reactive germinal centers and mantle zones. Around the mantle zone, there is an additional zone of somewhat larger cells corresponding to marginal zone cells. These larger cells extend into the overlying epithelium, forming a lymphoepithelium.

In accordance with the terminology of MALT in other body regions, MALT of the human nasolacrimal ducts was termed TALT and, in conjunction with CALT of the conjunctiva, EALT for eye-associated lymphoid tissue. Current analysis of EALT, as well as different epithelial cells of the lacrimal passage, is interesting with regard to the induction of tolerance in the nasolacrimal system and at the ocular surface.

Specific secretory immunity depends on a sophisticated cooperation between the mucosal B-cell system and an epithelial glycoprotein called the secretory component. The initial stimulation of Ig-producing B-cells is believed to occur mainly in organized MALT. It has become evident that considerable regionalization or compartmentalization exists in MALT, perhaps determined by different cellular expression profiles of adhesion molecules and/or the local antigenic repertoire. The antigenic stimulation of B-cells results in the generation of predominantly IgA-synthesizing blasts (an immature stage in cellular development before the appearance of the definitive characteristics of plasma cells) that leave the mucosae through efferent lymphatics, pass through the associated lymph nodes into the thoracic duct, and enter the circulation. The cells then return selectively to the lamina propria (nasolacrimal ducts) as plasma cells or memory B-cells by means of homing mechanisms and contribute to mucosal sIgA.

Absorption of Tear Fluid Components

Recent animal experiments in rabbits have indicated that the components of tear fluid are absorbed in the nasolacrimal passage and transported into the surrounding cavernous body that is subject to autonomic control and regulates tear outflow. Under normal conditions, tear fluid components are constantly absorbed into the blood vessels of the surrounding cavernous body. These vessels are connected to the blood vessels of the outer eye and could act as a feedback signal for tear fluid production (Figure 3), which ceases if these tear components are not absorbed.

2

1

Figure 3 The normally constant absorption of tear fluid components into the blood vessels of the surrounding cavernous body of the nasolacrimal ducts and their transport to the lacrimal gland by blood vessel connections (1) could be a feedback signal for tear fluid production (2). Reproduced from Paulsen, F. P., Schaudig, U., and Thale, A. B. (2003). Drainage of tears: Impact on the ocular surface and lacrimal system. Ocular Surface 1: 180–191.

Conclusions

The human efferent tear ducts are part of the lacrimal system. They consist of the upper and the lower lacrimal canaliculi, the lacrimal sac, and the nasolacrimal duct. As a draining and secretory system, the nasolacrimal ducts play a decisive role in tear transport and nonspecific immune defense. In this context, an active lacrimal pump mechanism that functions by contraction of the orbicularis eye muscle has the major impact on tear transport from the ocular surface into the lacrimal sac. From here, tears are transported by a wringing-out mechanism governed by the helical arrangement of fibrillar structures within the vascular system surrounding the lacrimal sac and nasolacrimal duct, the action of epithelial secretion products such as mucins, TFF peptides, surfactant proteins as well as probably others, and physical factors such as capillarity, gravity, respiration, and evaporation. Moreover, components of the tear fluid are absorbed by the epithelium of the nasolacrimal passage and transported into the surrounding vascular system of the lacrimal sac and nasolacrimal duct. This system is comparable to a cavernous body that is subject to autonomic control and also regulates tear outflow from the sac into the inferior meatus of the nose. TALT is present in the efferent tear ducts, displaying the cytomorphological and immunophenotypic features of mucosa-associated tissue MALT.

See also: Adaptive Immune System and the Eye: Mucosal Immunity; Adaptive Immune System and the Eye: T Cell-Mediated Immunity; Conjunctiva Immune Surveillance; Conjunctival Goblet Cells; Defense Mechanisms of Tears and Ocular Surface; Inflammation of the Conjunctiva; Lacrimal Gland Overview; Ocular Mucins; Overview of Electrolyte and Fluid Transport Across the Conjunctiva.

Further Reading

Amrith, S., Goh, P. S., and Wang, S-C. (2007). Lacrimal sac volume measurement during eyelid closure and opening. Clinical and Experimental Ophthalmology 35: 135–139.

Ayub, M., Thale, A., Hedderich, J., Tillmann, B., and Paulsen, F. (2003). The cavernous body of the human efferent tear ducts functions in regulation of tear outflow. Investigative Ophthalmology and Visual Science 44: 4900–4907.

Barishak, Y. R. (2001). Embryology of the Eye and Its Adnexa. Basel: Karger.

Bernal-Sprekelsen, M., Alobid, I., Ballesteros, F., et al. (2007). Dacryocystorhinostomy in children. In: Weber, R. K., Keerl, R., Schaefer, S. D., and Della Rocca, R. C. (eds.) Atlas of Lacrimal Surgery, pp. 69–71. Berlin: Springer.

Bra¨uer, L. and Paulsen, F. P. (2008). Tear film and ocular surface surfactants. Journal of Epithelial Biology and Pharmacology 1: 62–67.

Paulsen, F. (2003). The human nasolacrimal ducts. Advances in Anatomy, Embryology, and Cell Biology 170: 1–106.

Paulsen, F. (2006). Cell and molecular biology of human lacrimal gland and nasolacrimal duct mucins. International Review of Cytology 249: 229–279.

Paulsen, F. (2007). Pathophysiological aspects of PANDO, dacryolithiasis, dry eye, and punctum plugs. In: Weber, R. K., Keerl, R., Schaefer, S. D., and Della Rocca, R. C. (eds.) Atlas of Lacrimal Surgery, pp. 15–27. Berlin: Springer.

Paulsen, F. and Berry, M. (2006). Mucins and TFF peptides of the tear film and lacrimal apparatus. Progress in Histochemistry and Cytochemistry 41: 1–53.

Paulsen, F., Fo¨ge, M., Thale, A., Tillmann, B., and Mentlein, R. (2002). Absorption of lipophilic substances from tear fluid by the epithelium of the nasolacrimal ducts. Investigative Ophthalmology and Visual Science 43: 3137–3143.

Paulsen, F. P., Schaudig, U., and Thale, A. B. (2003). Drainage of tears: Impact on the ocular surface and lacrimal system. Ocular Surface 1: 180–191.

Paulsen, F., Thale, A., Hallmann, U., Schaudig, U., and Tillmann, B. (2000). The cavernous body of the human efferent tear ducts – function in tear outflow mechanism. Investigative Ophthalmology and Visual Science 41: 965–970.

Glossary

Conductive keratoplasty (CK) – Refractive surgery that uses heat from radio waves to shrink the collagen in the cornea. It is useful for patients with hyperopia and presbyopia.

Dry eye syndrome (DES) – Lack of quantity or quality of tears that lubricate the ocular surface.

Disodium ethylenediaminetetraacetic acid (EDTA) – Chemical that chelates calcium.

Descemet’s stripping automated endothelial keratoplasty (DSAEK) – Surgical procedure where the Descement’s basement membrane and endothelium of the host are removed and replaced with a thin posterior donor cornea lenticule in its place.

Hyperopia – Disorder of vision where the eye focuses images behind the retina instead of on it so that distant objects can be seen better than near objects.

Lamellar keratoplasty (LK) – Replacement of damaged or diseased anterior corneal stroma and Bowman’s membrane with donor material.

Laser-assisted in situ keratomileusis (LASIK) –

Refractive surgery that uses a laser to reshape the cornea.

Laser-assisted subepithelial keratomileusis (LASEK) – Refractive surgery that uses a laser to reshape the anterior cornea.

Laser thermokeratoplasty (LTK) – Refractive surgery using a mid-infrared laser shrinks the collagen of the corneal periphery.

Penetrating keratoplasty (PK) – Corneal transplant using the entire cornea from a donor.

Photorefractive keratectomy (PRK) – Refractive surgery where the corneal epithelium is removed and the stroma reshaped.

Phototherapeutic keratectomy (PTK) – Procedure where the corneal epithelium is removed and an excimer laser is used to smooth the surface of the cornea.

Radial keratotomy (RK) – Refractive surgery in which radial incisions are made in the cornea from the pupil to cornea.

Scheimpflug imaging – It measures central corneal thickness and anterior chamber depth.

Anatomy of the Layers

The cornea, often referred to as the window of the eye, is covered by the precorneal tear film, and provides a smooth, transparent medium for light rays to pass through. The average cornea measures approximately 12 mm horizontally and 11 mm vertically and seamlessly joins with the opacified sclera at its periphery. The normal cornea has five layers (epithelium, Bowman’s membrane, stroma, Descemet’s membrane, and endothelium), and has an approximate average central thickness of 540 mm.

Epithelium

The corneal epithelium is composed of approximately 5–6 rows of stratified squamous epithelial cells. It is these cells in this configuration, along with the overlying tear film that help create the smooth, clear surface. The tight junctions between epithelial cells help to prevent the penetration of microbes and fluid into the corneal stroma.

Epithelial cells are continuously being created by the basal limbal stem cells. New cells slowly migrate to the corneal surface where devitalized cells are lost and washed away in the tear film. The entire process takes approximately 2 weeks.

Epithelial Basement Membrane

Posterior to the epithelium of the cornea is the proteinacous epithelial basement membrane. Although only an50-nm thick membrane, the importance of this layer to maintaining a compact, clear, thin anterior corneal surface is obvious when dysfunction occurs, such as in map-dot- fingerprint dystrophy (corneal epithelial basement membrane dystrophy). The thickened basement membrane present in this condition can be visualized on slit-lamp examination and it is the dysfunction of this layer that often leads to recurrent corneal erosions.

Bowman’s Membrane

Beneath the epithelial basement membrane lies the acellular Bowman’s membrane. This membrane marks the transition from the epithelium to the cornea stroma.

Stroma

A majority of the cornea (approximately 90% of the full corneal thickness) is the stroma. The stroma is composed of a mixture of lamellae of collagen fibrils, proteoglycans, and keratocytes. The collagen and proteoglycans are produced by the keratocytes, which are dispersed throughout the stoma. The arrangement of collagen fibrils in the stroma plays an important role in maintaining corneal transparency.

Descemet’s Membrane

The endothelial basement membrane is termed Descement’s membrane. This basement membrane is continually laid down throughout life by the corneal endothelium and is approximately 4-mm thick at birth and approximately 12-mm thick in adulthood. Descemet’s membrane is firmly attached to the endothelium by hemidesmosomes (Figure 1).

Endothelium

The corneal endothelium is only a single cell-layer thick. These hexagonal cells are of vital importance to maintaining the clarity of the cornea. The endothelial cells lie adjacent to the anterior chamber and work to help maintain the relative dehydrated state of the cornea. The electrolyte pump of the endothelial cells creates an osmotic gradient that draws fluid from the stromal tissue.

Unlike the corneal epithelium, the endothelium is not replaced by limbal stem cells when damaged. The average person is born with approximately 3500 cells mm 2, which declines to approximately 2500 cells mm 2 in the eighth decade of life. When endothelial cells are lost or lose functionality, adjacent endothelial cells must enlarge or change shape to attempt to maintain deturgescence. Once a significant portion of endothelial cells are damaged or not functioning properly, corneal edema ensues. The loss of endothelial function can be evaluated by slit-lamp

exam, corneal thickness measurements, or through visualization with confocal microscopy, where the number, size, and shape of endothelial cells can be evaluated (Figure 2).

Function

The cornea performs vital functions as a protective barrier and as an optically clear media.

Protective Barrier

The corneal tear film is of vital importance to protecting the eye from invading pathogens. However, in addition to the tear film, it is the tight junctions between the posterior epithelial cells that act as the final barrier in preventing the entrance of microbes into the corneal stroma. This barrier also acts to prevent the inflow of excessive fluid to the stoma from the outside environment.

Transparency

There are three main attributes of the cornea that allow the tissue to maintain its transparency.

First, the water content of the cornea tissue must be maintained at approximately 78%. This water content is dependent on both the epithelial and endothelial cells. The epithelium functions as the physical anterior barrier to the influx of excessive fluid into the corneal stroma. The endothelium is not only a posterior physical barrier to the influx of fluid into the corneal stroma but also uses its sodium–potassium pump to create an osmotic gradient that draws water out of the corneal stroma.

Second, it is the compact arrangement and concentration of collagen, keratocytes, and extracellular matrix within the stroma that limits the scattering of light passing through the tissue.

Third, the lack of blood vessels in the cornea allows the light rays that pass through the clear tissue to not be

obscured, refracted, or diffracted in any way by blood vessels. The lack of blood vessels also limits the effect that egress or ingress of fluid into or out of the blood vessels could have on corneal deturgescence (Figure 3).

Disease Processes

The disease processes affecting the cornea are extensive. The following review is not meant as an exhaustive list, but rather as an introduction to many of the more commonly observed or discussed pathologies in clinical practice. The use of slit-lamp biomicroscopy to clearly identify which corneal layers are affected by the disease process is of vital importance to the corneal surgeon when choosing among the available medical and surgical treatment options.

Epithelial Disease

Epithelial staining patterns

The use of vital dyes is required to discern the disease process affecting the corneal epithelium. These dyes include fluorescein, rose bengal, and lissamine green. Fluorescein will stain areas with an epithelial defect, while rose bengal and lissamine green will stain areas of devitalized epithelium.

Figure 3 Loss of corneal transparency from a mucopolysaccharidosis. The peripheral cornea remains opacified, while the central cornea is transparent following a penetrating keratoplasty.

By analyzing the staining pattern on the corneal surface, the possible etiology of the disease process (Figure 4) may become apparent (Table 1).

Epithelial iron deposition

Often, the deposition of iron can be visualized on slit-lamp examination of the corneal epithelium. The deposition of