IV - Nervous System

Editors: Mills, Stacey E.

Title: Histology for Pathologists, 3rd Edition

Copyright 2007 Lippincott Williams & Wilkins

> Table of Contents > V - Head and Neck > 13 - Normal Eye and Ocular Adnexa

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13

Normal Eye and Ocular Adnexa

Gordon K. Klintworth

Thomas J. Cummings

Introduction

The eye and surrounding tissues are subject to a wide variety of primary ocular and systemic disease processes. An understanding of ocular anatomy will enable the general surgical pathologist to appreciate morphologic abnormalities and will facilitate the diagnosis of many of the pathologic conditions affecting those structures. Similar to other specimens received by the surgical pathologist, in some cases a discussion with the ophthalmologist who is submitting the tissue is important for proper handling, sectioning, and processing of the tissue. Proper handling of the tissue is required so as to not artifactually mask the diagnostic histologic features, such as the common age-related arcus lipoides.

This chapter presents an overview of the normal histology of the eye and ocular adnexa. Several excellent texts are available for more detailed information on ocular anatomy and development (1,2,3,4,5).

The eye is roughly spherical in shape and external measurements are routinely obtained in three dimensions. In the adult, the anterioposterior plane of the eye measures approximately 24 mm, whereas the vertical and the horizontal dimensions are both about 23 to 23.5 mm. Located midway between the anterior and posterior poles of the eye is the equator of the globe.

Several external landmarks allow the pathologist to orient the globe and to determine whether an eye is from the right or the left side (Figure 13.1). By establishing the nasal (medial) and temporal (lateral) sides of the globe and the superior surface of the eye, the side of the eye can easily be deduced. The six extraocular muscles (four rectus and two oblique muscles) that arise in the posterior orbit and run forward to insert upon the sclera are important in this regard. The rectus muscles arise from a fibrous ring at the apex of the orbit, the annulus of Zinn, and are enveloped by a fascial membrane that creates a cone-shaped structure posterior to

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the globe. The levator palpebrae superioris also arises at the orbital apex and extends anteriorly to the eyelids. Of the extraocular muscles, only the inferior oblique has a muscular insertion upon the sclera; the other muscles have tendinous insertions. The extraocular muscle insertions are usually removed by the surgeon when the globe is excised (enucleated), but they are frequently present on eyes obtained postmortem. The superior and inferior oblique muscles are most useful in orientating the globe. The tendinous insertion of the superior oblique muscle behind the superior rectus muscle insertion indicates the top of the eye. The inferior oblique muscle inserts on the sclera temporally in the horizontal meridian, and its fibers run inferiorly toward the back of the orbit. The optic nerve is also useful in assessing orientation because it exits the globe slightly nasal to the posterior pole of the eye. Adjacent to the optic nerve, the prominent long posterior ciliary arteries course through the superficial sclera in opposite directions in a horizontal plane. Anteriorly, the dimensions of the cornea may be helpful in topographic orientation. In the adult, the cornea is elliptical in shape with its horizontal diameter being slightly greater than its vertical breadth. In young children, this difference is less apparent.

Figure 13.1 This drawing depicts the right eye as seen from behind. Several external landmarks are useful in determining orientation of the globe. The optic nerve (a) is located approximately 1 mm inferior to and 3 mm nasal to the posterior pole of the eye. The long posterior ciliary arteries (b) are located in the horizontal plane, and four vortex veins (c) exit the sclera posteriorly. The superior oblique muscle (d) inserts on the top of the globe, whereas the inferior oblique muscle (e) inserts temporally, and its fibers run posteriorly and nasally. The rectus muscles (f) insert horizontally, inferiorly, and superiorly. The approximate location of the macula (x), the part of the retina responsible for the most distinct vision, is slightly temporal to the optic nerve. (Reproduced with permission from:

Hogan MJ, Alvarado JA, Weddell JE. Histology of the Human Eye: An Atlas and Text. Philadelphia: WB Saunders; 1971.

)

Figure 13.2 This photomicrograph of a histologic section of an eye from a rhesus monkey illustrates the major tissue layers of the eye, the lens, the vitreous humor body, and the spaces of the anterior and posterior chambers. (Reproduced with permission from:

Bloom W, Fawcett DW. A Textbook of Histology. 12th ed. New York: Chapman and Hall; 1994.

)

The eye is traditionally described as having three tissue layers that surround the vitreous humor, the lens, and the spaces of the anterior and posterior chambers (Figure 13.2). The outermost part of the eye is composed of the transparent cornea and the opaque sclera. The ocular middle layer is made up of the iris, ciliary body, and the choroid. The innermost retina is in direct contact with the vitreous humor body.

Cornea

The transparent cornea occupies one-sixth of the anterior surface of the globe and refracts the entering light. Although individual variation is common, the cornea measures approximately 11.7 mm in the horizontal plane and 10.6 mm in the vertical plane. Centrally, the cornea is about 0.5 mm thick, but peripherally it thickens to about 0.67 mm. Histologically, the cornea consists of six distinct layers: (a) the epithelium; (b) the basal lamina of the epithelium; (c) Bowman's layer; (d) the stroma; (e) Descemet's membrane; and (f) the endothelium (Figure 13.3).

Figure 13.3 The stratified squamous epithelium of the cornea (arrow) overlies the basal lamina and Bowman's layer. The clefts within the collagenous stroma (double arrows) represent artifacts of tissue processing. No blood vessels or lymphatics are normally present within the cornea. Descemet's membrane and the corneal endothelium are located just posterior to the stroma. (H&E, 33.)

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The corneal epithelium, which is composed of stratified nonkeratinized squamous cells, is about five cell layers thick centrally. The peripheral cornea is often twice as thick. The basilar epithelial cells are polygonal in shape; and, as they become displaced to the corneal surface during differentiation, a more flattened appearance is acquired. In the normal cornea, even the most superficial epithelial cells retain their nuclei. Mitotic figures are uncommon in the epithelium but are observed in the basal cells occasionally. Some Langerhans cells are present within the corneal epithelium, especially peripherally (6). Apoptosis is also uncommonly seen in the epithelium of the normal cornea. Langerhans cells are most readily identified by special histochemical and immunohistochemical methods and are not normally recognizable in routinely stained tissue sections.

The corneal epithelium rests upon a basal lamina, which is difficult to see in hematoxylin and eosin (H&E) stained tissue sections. Staining with the periodic acid-Schiff (PAS) reaction makes this layer apparent (Figure 13.4). In certain pathologic conditions, the epithelial basal lamina assumes an intraepithelial location.

Bowman's layer is an acellular structure located just posterior to the epithelial basal lamina (Figure 13.4). It is approximately 8 to 14 m thick. As shown by transmission electron microscopy, Bowman's layer is not a true basement membrane but is composed of randomly oriented delicate collagen fibers. The anterior face of Bowman's layer ends distinctly at its junction with the epithelial basal lamina. Posteriorly, Bowman's layer merges inconspicuously with the underlying corneal stroma. Unmyelinated sensory nerves reach the epithelium from the stroma after crossing Bowman's layer. However, nerve processes are difficult to detect in the cornea in standard tissue sections, even with the use of special histologic techniques.

The stroma accounts for approximately 90% of the cornea's thickness. It is composed of numerous layers of collagen fibers embedded in a proteoglycan-rich extracellular matrix, and the anterior and posterior portions of the cornea have several differences. The stroma contains keratan sulfate proteoglycans (lumican, keratocan, mimecan), as well as a galactosaminoglycan-rich proteoglycan (decorin). Transmission electron microscopy has disclosed that the corneal collagen fibers are regularly spaced and of a uniform diameter; this arrangement contributes to the transparency of the cornea. The corneal fibroblasts (keratocytes) are surrounded by the stromal collagen lamellae. Other cell types are seldom identified in tissue sections of the normal corneal stroma, but rarely an occasional mononuclear leukocyte or granulocyte may be present. The normal cornea lacks blood vessels, and its nutrition is obtained from an arterial plexus at the junction of the cornea and sclera and from direct contact with the aqueous humor of the anterior chamber. In tissue sections of routinely processed formalin-fixed corneas, clefts are almost invariably present between the collagen lamellae. Initially interpreted as lymphatic channels by early histologists, these clefts are artifacts of tissue processing. Lymphatic vessels are not present in the normal cornea.

Descemet's membrane, a true basal lamina elaborated by the underlying corneal endothelial cells, begins to form

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during fetal life. At birth, it is approximately 3 to 4 m thick (Figure 13.5). Basal laminar material is continuously added to the posterior part of Descemet's membrane throughout life so that by adulthood, this structure attains a thickness of approximately 10 to 12 m. The fetal and postnatal regions of Descemet's membrane differ ultrastructurally. This difference is occasionally discernible by light microscopy.

Figure 13.4 The corneal epithelium rests upon a thin basal lamina (arrow), which is prominent in this section following periodic acid-Schiff staining. The acellular band directly underneath the basal lamina is Bowman's layer (double arrows) (PAS, 132).

The corneal endothelium (Figure 13.5) is directly exposed to the aqueous humor in the anterior chamber. Although this cell layer does not line blood vessels or lymphatic spaces, the term endothelium is firmly entrenched in the literature. These cells function as an osmotic pump to regulate a necessary state of stromal dehydration that preserves corneal clarity. Endothelial decompensation results in corneal edema and diminished optical transparency. The corneal endothelium has been shown by immunohistochemistry to be S-100 protein positive, a finding supportive of other evidence suggesting a neural crest origin (7). They react with the monoclonal antibody 2B4.14.1, which recognizes the renal Tamm-Horsfall glycoprotein (THGP) antigen, raising the possibility that the cornea expresses a molecule with homeostatic properties similar to that ascribed to THGP (8). The endothelial cells of the cornea normally form a single flattened layer and, virtually, never regenerate by mitosis in human eyes. Under pathologic conditions (epithelial ingrowth and posterior polymorphous corneal dystrophy), cytokeratin-containing squamous cells replace the endothelium and form a layer that is more than one cell thick.

After the second decade of life, age-related focal excrescences (Hassall-Henle warts) commonly form on the peripheral part of Descemet's membrane (Figure 13.6). Virtually identical focal thickenings occur on the central part of Descemet's membrane (corneal guttae) under pathologic circumstances and most notably in Fuchs's corneal dystrophy. The presence of excrescences on Descemet's membrane in tissue sections of corneal buttons removed at penetrating keratoplasty (full-thickness corneal transplant) is always abnormal. Hassall-Henle warts are too peripheral in location to be present in a surgically excised corneal button.

Figure 13.5 A thin monolayer of corneal endothelial cells (arrow) is adjacent to Descemet's membrane (double arrows). These cells are in direct contact with the aqueous humor of the anterior chamber (H&E, 132).

Figure 13.6 Descemet's membrane (single arrows) is located immediately posterior to the corneal stroma. The excrescences on the peripheral portion of Descemet's membrane (Hassall-Henle warts) (double arrows) represent an aging change. Descemet's membrane also thickens with age. (H&E, 132.)

Corneal epithelium and endothelium are prone to being artifactitiously rubbed-off during prosection of the tissue, and it is important to distinguish this artifact from the true loss of corneal epithelium and endothelium.

Sclera

The sclera, which accounts for approximately five-sixths of the surface area of the eye, begins at the periphery of the cornea and extends posteriorly to the optic nerve. The sclera's relatively rigid nature protects the eye from trauma and helps maintain intraocular pressure. Anteriorly, the sclera is visible underneath the transparent conjunctiva and is normally white in adults. The sclera varies in thickness, being about 0.8 mm thick near its junction with the cornea. At the insertions of the four rectus muscles (approximately 5 to 8 mm posterior to the corneoscleral junction), the sclera is at its thinnest, measuring approximately 0.3 mm. From this point posteriorly, the sclera gradually thickens and attains its maximal width of about 1.0 mm adjacent to the optic nerve.

The sclera has three components: the episclera, the stroma, and the lamina fusca. The episclera, its most superficial part, is located between the fibrous structure that envelopes the globe (Tenon's capsule) and the underlying scleral stroma with which it merges. The episclera is composed of loosely arranged collagen fibers and fibroblasts embedded in an extracellular matrix. Occasional melanocytes and mononuclear leukocytes are also present. Anteriorly, the episclera is richly vascularized.

The largest component of the sclera is its stroma, which consists of fibrous bands of collagen, occasional elastic fibers, and scattered fibroblasts (Figure 13.7). The corneal

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and scleral stroma appear similar at the light microscopic level; but, when viewed by transmission electron microscopy, the individual collagen fibers within the sclera vary in diameter and are randomly arranged, in contrast to the orderly packed corneal collagen fibers of uniform diameter. This largely accounts for the opaque nature of the sclera.

Figure 13.7 The scleral stroma is predominantly composed of collagen fibers that vary in diameter and are in haphazard array. Scattered fibroblasts occur between the collagen bundles. (H&E, 100.)

Although the scleral stroma is relatively avascular, blood vessels, as well as accompanying nerves and scattered melanocytes, are present in perforating emissarial canals (Figure 13.8). The anterior ciliary arteries perforate the sclera near the insertion of the rectus muscles. Venous channels draining the iris, ciliary body, and choroid (vortex veins) exit the sclera several millimeters posterior to the equator of the eye. The posterior ciliary arteries pass through the sclera near the optic nerve. In some individuals, a nerve in an emissarial canal near the corneoscleral junction may be prominent and attain a diameter of 1 to 2 mm. The nodular appearance of this so-called nerve loop of Axenfeld may mimic a neoplasm or conjunctival cyst clinically (9). To the unwary surgical pathologist, this totally normal nerve bundle may be mistaken for a neurofibroma (10).

Figure 13.8 This figure illustrates a blood vessel that penetrates the sclera and extends to the prominently vascularized choroid through an emissarial canal (single arrows). Pigmented melanocytes are also present. The fibers of the inferior oblique muscle are present at the site of insertion upon the outer sclera (double arrows). (H&E, 50.)

The innermost layer of the sclera, the lamina fusca, contains loose collagen fibers, fibroblasts, and scattered melanocytes. It represents a region of transition between the sclera and the underlying choroid. The sclera is weakly attached to the choroid below by thin fibers of collagen.

With increasing age, several histologic changes occur in the sclera. Calcium may deposit diffusely between the individual collagen fibers throughout the entire scleral stroma. Localized abnormalities, known as senile scleral plaques, may occur just anterior to the insertion of the lateral or horizontal rectus muscles. These lesions are characterized by decreased stromal cellularity, abnormal collagen, and, in advanced cases, calcification (11).

Corneoscleral Limbus

The corneoscleral limbus, or junction, is not a distinct anatomic site but is a significant landmark clinically. Most surgical procedures on the anterior part of the eye are accomplished after access via an incision in the limbal area. For purposes of discussion, the trabecular meshwork and Schlemm's canal will be considered as part of the corneoscleral limbus.

The limbus is approximately 1.5 to 2.0 mm wide, and separate layers of the cornea merge with components of the sclera or conjunctiva in this area (Figure 13.9). The squamous epithelium of the cornea extends centrifugally beyond the limbus until it meets the epithelium of the bulbar conjunctiva. At the limbus, Bowman's layer of the cornea blends into the subepithelial tissues of the conjunctiva, and the corneal and scleral stroma become continuous with each other. Descemet's membrane abruptly terminates in the limbal region and gives rise to the clinically significant landmark known as Schwalbe's ring. In about 15% of eyes, a prominent area of thickening is identified histologically at this site (Figure 13.10) (2). Immediately adjacent to Schwalbe's ring is the most anterior aspect of the trabecular meshwork. Both the trabecular meshwork and Schlemm's canal constitute the apparatus responsible for the removal of aqueous humor from the eye (Figure 13.11). Aqueous humor drainage occurs in the angle between the anterior surface of the iris and the sclera. Histologically, the meshwork appears as a collection of finely branching and delicately pigmented connective tissue bands. The cells, which line the trabecular meshwork, are continuous with the corneal endothelium. Posteriorly, the trabecular meshwork extends to a roughly triangular-shaped projection of scleral connective tissue, known as the scleral spur.

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Figure 13.9 The corneoscleral limbus represents the junction of the peripheral cornea with the anterior sclera and is not a distinct anatomic site. Clinically, the limbus is an important landmark. The conjunctiva of the limbus (A) is composed of epithelium (1) and stroma (2). The thin connective tissue layer of Tenon's capsule (B) overlies the episclera (C). The corneal and scleral stroma merge gradually in the area marked D. Vessels of the conjunctival stroma (a, b), episclera (c), and limbal plexus (d, e) are illustrated. The projection of collagen fibers known as the scleral spur (f) merges with the smooth muscle fibers of the ciliary body (g). Schlemm's canal (h) and the trabecular meshwork (i, j) are responsible for removal of aqueous humor from the eye. Occasionally, processes from the iris (k) insert upon the trabecular meshwork. Bowman's layer (arrow) and Descemet's membrane (double arrows) both terminate in the area of the limbus. (Reproduced with permission from:

Hogan MJ, Alvarado JA, Weddell JE. Histology of the Human Eye: An Atlas and Text. Philadelphia: WB Saunders; 1971.

)

Figure 13.10 Schwalbe's ring is a significant clinical landmark in the limbal area and represents the peripheral termination of Descemet's membrane. Prominent Schwalbe's rings (arrow) are identified histologically in about 15% of eyes. (H&E, 80.)

Figure 13.11 A. Located in the angle of the anterior chamber is Schlemm's canal (SC) and the trabecular meshwork (arrow). Schlemm's canal is an endothelial channel that enables aqueous humor to drain from the eye. Aqueous humor reaches Schlemm's canal after percolating through the connective tissue strands of the trabecular meshwork. (H&E, 66.) B. Structures within and near the angle of the anterior chamber are depicted in this drawing. In this illustration, Schlemm's canal (a) has two channels, one of which is in communication with a small collecting channel (b). The collecting channel is intimately associated with the limbal part of the trabecular meshwork (c). The scleral spur (d) is closely associated with the trabecular meshwork. Descemet's membrane terminates peripherally in the area denoted e and g. Some components (f) of the trabecular meshwork arise at the ciliary body (CB). Isolated strands of meshwork merge with a nearby process (h) from the anterior surface of the iris. A muscle of the ciliary body (i) attaches to the trabecular meshwork (arrows). The corneal endothelium merges with endothelial cells of the meshwork (j). (Reproduced with permission from:

Hogan MJ, Alvarado JA, Weddell JE. Histology of the Human Eye: An Atlas and Text. Philadelphia: WB Saunders; 1971.

)

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Located slightly anterior and superficial to the trabecular meshwork is Schlemm's canal, an endothelial-lined venous channel that completely encircles the limbus. Because Schlemm's canal sometimes gives off smaller branches, two lumens are occasionally seen on histologic sections of the anterior chamber angle. Although the trabecular meshwork and Schlemm's canal appear to be in intimate contact in tissue sections, they are separated from each other by a thin layer of connective tissue and separate endothelial linings. Aqueous humor percolates among the delicate beams of the trabecular meshwork before becoming transported to Schlemm's canal. Ultrastructural examination of this region discloses giant cytoplasmic vacuoles in the endothelial lining of Schlemm's canal, adjacent to the trabecular meshwork. These vacuoles are thought by some to contain fluid in the process of being transported from the trabecular meshwork into the lumen of Schlemm's canal (12). Once in Schlemm's canal, aqueous humor drains into the episcleral venous plexus by way of numerous small collector channels. Prolonged obstruction to the outflow of aqueous humor results in increased intraocular pressure and glaucoma.

Conjunctiva, Caruncle, and Plica Semilunaris

The conjunctiva is a thin continuous mucous membrane lining the inner surface of the eyelids and much of the anterior surface of the eye. In addition to its protective function, the conjunctiva allows the eyelids to move smoothly over the globe. The conjunctival epithelium is composed of two to five layers of columnar cells and rests upon a basal lamina. Within the conjunctival epithelium are goblet cells that secrete mucoid material that becomes incorporated into the tear film (Figure 13.12). Melanocytes are present in the basal epithelial layers and, like melanocytes in the skin, transfer melanosomes into adjacent epithelial cells. These pigmented epithelial cells are numerous in dark-skinned individuals (Figure 13.13). The loose, fibrovascular subepithelial connective tissue of the conjunctival stroma normally contains nerve cells, melanocytes, and accessory lacrimal glands. Lymphoid follicles with germinal centers reside in the conjunctiva (Figure 13.14), particularly in areas where the conjunctiva lining the inner surface of the eyelid merges with the portion covering the eyeball (superior and inferior fornices); scattered lymphocytes are not unusual within the conjunctiva. Hence, their presence is not indicative of chronic conjunctivitis unless both plasma cells and significant numbers of lymphocytes are present. Three distinct areas of the conjunctiva are recognized (Figure 13.15): the palpebral conjunctiva, the bulbar conjunctiva, and the conjunctiva lining the fornices.

The morphologic attributes of the conjunctiva vary in different parts of this tissue. Although goblet cells exist throughout the epithelium of the bulbar conjunctiva, they

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are more common in the inferior and nasal parts. Goblet cells are particularly abundant in the forniceal regions. The conjunctival stroma is thickest in the fornices and bulbar areas and thinnest in the palpebral conjunctiva and at the corneoscleral limbus, where small conjunctival papillae, known as the pallisades of Vogt, are evident. The palpebral conjunctiva is firmly attached to the inner surface of the eyelids, but the bulbar conjunctiva is loosely adherent to the underlying sclera by thin connective tissue strands.

Figure 13.12 Goblet cells (arrows) are prominent in this section of conjunctival epithelium. Scattered mononuclear cells are often present in apparently healthy individuals in the underlying conjunctival stroma. (H&E, 66.)

Figure 13.13 In dark-skinned individuals, the basal layers of the conjunctival epithelium are pigmented (arrows) (H&E, 160).

Figure 13.14 A small lymphoid follicle and island of accessory lacrimal tissue are present in the stroma of the palpebral conjunctiva (H&E, 25).

Figure 13.15 The conjunctiva can be divided into three parts. The palpebral conjunctiva (arrow) lines the posterior surface of the eyelid. The bulbar conjunctiva (double arrows) extends from the limbus over the anterior sclera. The bulbar and palpebral conjunctiva converge upon the conjunctiva of the superior and inferior fornices (triple arrows). (H&E, 2.5.)

The palpebral conjunctiva, which lines the posterior surface of the eyelids, extends from the fornices to the mu-cocutaneous junction at the eyelid margins, where the epithelium of the conjunctiva merges abruptly with the epidermis of the anterior surface of the eyelids. The palpebral conjunctiva contains several infoldings of epithelium (crypts of Henle). Islands of accessory lacrimal glands that are morphologically identical to the main tear-producing gland within the orbit occur within the palpebral conjunctiva. The subconjunctival tissue of the upper fornix may contain over 40 such glands, but fewer than 10 accessory lacrimal glands are present in the lower fornix (glands of Krause). The upper eyelids have approximately two to five accessory lacrimal glands (glands of Wolfring) located at the superior aspect of the tarsus. The bulbar conjunctiva begins at the limbus, at which point the corneal epithelium gradually becomes replaced by conjunctival epithelium and continues over the sclera to the superior and inferior fornices. There, the conjunctiva is thrown into small folds before becoming the palpebral conjunctiva.

Both the caruncle and plica semilunaris (semilunar fold) represent specialized segments of the conjunctiva (Figure 13.16). The caruncle is the nodular mass of fleshy tissue located in the medial interpalpebral angle of the eye. Its surface is covered by a stratified nonkeratinized squamous epithelium. The subepithelial stroma of the caruncle contains hair follicles, smooth muscle, sebaceous glands, adipose connective tissue, and, occasionally, accessory lacrimal glands and sweat glands. The plica semilunaris, an arc-shaped fold of conjunctiva located immediately lateral to the caruncle, is thought to be a vestigial remnant of the nictitating membrane of lower species. The histologic features of the plica semilunaris are similar to those in other areas of the conjunctiva, except that the epithelium contains abundant goblet cells and, rarely, cartilage is present within the stroma.

Figure 13.16 The caruncle and semilunar fold are specialized portions of the conjunctiva and are located in the medial interpalpebral angle of the eye. Before tears enter the lacrimal drainage apparatus through the lacrimal punctum, they accumulate at the medial canthus (lacrimal lake). The demarcation between the conjunctival and cutaneous portions of the eyelid is discernible clinically at the so-called gray line. The secretions of the meibomian glands (tarsal glands) reach the surface of the eyelids at small orifices. (Reproduced with permission from:

Newell FW. Ophthalmology: Principles and Concepts. 6th ed. St. Louis: CV Mosby; 1986.

)

The Uveal Tract

Located between the outer scleral covering and the inner retina is the uveal tract, which begins anteriorly as the iris, extends to the ciliary body, and then to the choroid posteriorly. The designated term uvea is derived from the Latin word uva (grape) because this portion of the eye was thought to somewhat resemble the dark color of a grape after the sclera and cornea are stripped from the globe.

The Iris

The iris is a thin diaphragm of tissue with a central opening, the pupil, which functions to regulate the amount of

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light reaching the retina (Figure 13.17). Muscles within the iris dilate or constrict the pupil in response to sympathetic or parasympathetic nerve impulses. The diameter of the iris is approximately 21 mm, whereas the diameter of the pupil ranges from 1 to 8 mm. The iris is thinnest at its point of attachment with the ciliary body peripherally, the iris root. Normally, the iris rests gently upon the crystalline lens and, therefore, bulges slightly forward. Structurally and developmentally, the iris consists of two main parts: the stroma and the posterior epithelial lining.

Figure 13.17 The iris is composed of stroma (S) and a posterior epithelial lining (PEL). The sphincter muscle (SM) of the iris is evident within the stroma. The pigmented posterior epithelial lining normally extends around the lip of the pupil anteriorly for a short distance. (H&E, 25.)

Numerous ridges and depressions may be identified in tissue sections of the anterior iris stroma. These correspond to the contraction folds and furrows seen on clinical examination. The anterior surface of the iris lacks a cellular lining. The stroma contains melanocytes, nerve cells, blood vessels, and smooth muscle in a loose connective tissue background. The color of the iris is due to the number of stromal melanocytes present. Lightly pigmented individuals with blue irises have relatively few stromal melanocytes. In contrast, darkly pigmented individuals with brown irises have numerous melanocytes within the iris stroma (Figure 13.18). In addition to melanocytes, melanosome-containing macrophages are also scattered within the iris stroma, particularly at the iris root. A thick collar of collagen fibers normally surrounds the blood vessels within the iris stroma. To the inexperienced observer, these normal vessels may appear to have arteriolosclerosis. In the pathologic process of iris neovascularization, thin-walled blood vessels, which lack such a collagenous coat, cover the anterior surface of the iris.

Figure 13.18 The color of the iris is due to the number of stromal melanocytes, which are more abundant in the stroma of an individual with a brown iris (left) than with a blue iris (right). The amount of pigment in the posterior epithelial lining is similar in irises of different color. Blood vessels in the iris stroma are normally surrounded by a thick collar of collagen fibers (arrows); this should not be confused as arteriolosclerosis. In contrast to the posterior surface of the iris, the anterior iris lacks a cellular lining. (Left, H&E, 66; right, H&E, 66.)

The sphincter muscle (sphincter pupillae), a bundle of circularly arranged smooth muscle innervated by parasympathetic nerves, acts to constrict the pupil. Located within the posterior stroma of the pupillary zone, the sphincter pupillae is nearly 1 mm wide. Radially oriented smooth muscle fibers with scattered cytoplasmic melanosomes are also located within the stroma of the iris (dilator pupillae). Innervated by sympathetic nerves, this muscle is active in pupil dilatation.

Posteriorly, the iris is lined by two separate but closely apposed epithelial layers derived from neuroectoderm. The cells of the anterior epithelial layer, which are in direct contact with the posterior aspect of the stroma, are continuous with smooth muscle fibers of the dilator pupillae; the sphincter pupillae are of similar developmental origin. The posterior iris pigment epithelial layer is in direct contact

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with the aqueous humor of the posterior chamber. The cytoplasm of both epithelial layers contains numerous melanosomes (approximately 1 m in diameter), which are larger than those of the iris stroma (diameter of about 0.5 m). The number of melanosomes in the iris epithelial layers does not vary significantly between lightly and darkly pigmented individuals. In persons with ocular and oculocutaneous albinism, the pigmented epithelia, as well as the stromal melanocytes, contain fewer melanin granules than in normal individuals. The pigmented epithelia of the iris normally extend around the lip of the pupil anteriorly for a short distance. In certain pathologic conditions, fibrovascular tissue on the anterior surface of the iris everts the pupillary margin and pulls the pigmented epithelia onto the anterior surface of the iris. This displaced pigmented epithelium may be apparent clinically and is known as ectropion uveae.

Figure 13.19 The lens and ciliary body are viewed from behind in this photograph. The ciliary body has two components: the pars plicata and the pars plana. The pars plicata contains about 70 sagitally oriented folds, or ciliary processes (arrow). The pars plicata gradually merges with the flat pars plana (arrowhead). (Reproduced with permission from:

Klintworth GK, Landers MB III. The Eye: Structure and Function. Baltimore: Williams & Wilkins; 1976.

)

Figure 13.20 A. The epithelium of the ciliary body has two distinct layers. The inner nonpigmented layer (arrow) is in direct contact with the aqueous humor of the posterior chamber (PC). The outer pigmented epithelial layer (double arrows) is adjacent to the underlying stroma. Acellular eosinophilic fibers attach to the crests of the nonpigmented epithelium of the pars plicata (zonules) (arrowheads). Zonules do not originate in the valleys between the ciliary processes (H&E, 132). B. Zonular fibers (arrows) span between the pars plicata of the ciliary body (right) and the lens (L) and hold the lens in place (H&E, 25).

The Ciliary Body

The middle segment of the uveal tract, the ciliary body, is located between the iris and the choroid. Situated interior to the anterior sclera, it is made up of two ring-shaped components: the pars plicata and the pars plana (Figure 13.19). The anteriormost aspect of the ciliary body, the pars plicata begins at the scleral spur and contains approximately 70 sagitally oriented folds (approximately 2 mm long and 0.8 mm high). Continuous with these folds, the flat pars plana, which is approximately 4 mm wide, merges posteriorly with the serrated anterior border of the retina (ora serrata). Both portions of the ciliary body consist of epithelium, stroma, and smooth muscle.

The ciliary epithelium embraces two distinct layers, both of which share a similar development derivation from neural ectoderm (Figure 13.20). The inner epithelial layer is virtually nonpigmented and is contiguous with the aqueous humor of the posterior chamber. At the ora serrata, the sensory retina converges into the nonpigmented ciliary epithelial monolayer, which extends anteriorly until it

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becomes the posterior epithelial layer of the iris. In contrast, the outer ciliary epithelial layer is pigmented and unites with the retinal pigment epithelium at the ora serrata. The pigmented epithelium of the ciliary body overlies a periodic acid-Schiff (PAS) positive basal lamina that is closely adherent to the adjacent stroma. The basal lamina of the pigmented epithelium can become conspicuously thickened in diabetes mellitus. Acellular fibers, known as zonules (Figure 13.20), attach the crests of the nonpigmented ciliary epithelium in the pars plicata to the capsule of the crystalline lens.

Figure 13.21 The pars plicata of the ciliary body changes with age. A. In infancy the stroma of the ciliary processes is sparse (arrow). B. The stroma continues to expand until adulthood; and, with advancing age, the ciliary processes become hyalinized (double arrows). (A, H&E, 40; B, H&E, 40.)

The stroma of the ciliary body, composed of fibroblasts, blood vessels, nerve cells, and melanocytes, is most abundant in the ciliary processes of the pars plicata and least plentiful in the valleys between these processes and in the pars plana. During infancy, the stroma of the ciliary body is sparse (Figure 13.21, left), but it expands until adulthood. With advanced age, the ciliary body stroma becomes hyalinized (Figure 13.21, right) and frequently calcifies.

The smooth muscle of the ciliary body (Figure 13.22) forms three distinct bundles. The outermost muscle runs in a longitudinal, or meridonal, direction, whereas the middle layer contains radially oriented fibers and the innermost muscle cells are aligned in a circular fashion. In routinely processed globes, histologic differentiation of these three muscular layers is difficult. Muscles of the ciliary body attach in large part to the scleral spur. The ciliary muscle assists in accommodation. As it contracts, the ciliary body extends forward, reducing pressure on the zonules and enabling the lens to become less concave and thereby increasing its refractive power.

Choroid

The richly vascularized choroid (Figure 13.23) extends from the ciliary body to the optic nerve. Its inner aspect is firmly adherent to the retinal pigment epithelium. The outer surface of the choroid is loosely attached to the overlying sclera. Bruch's membrane delineates the choroid from the overlying retinal pigment epithelium and is approximately 2 to 4 m thick. Although Bruch's membrane appears as a thin eosinophilic layer in tissue sections, ultrastructural analysis has disclosed it to be composed of five distinct layers: the basal lamina of the overlying retinal pigment epithelium, a collagenous layer, an elastic fiber-rich component, another collagenous portion, and the

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basal lamina of the endothelial cells of the underlying capillary network (choriocapillaris). Located in the innermost choroidal stroma adjacent to Bruch's membrane, the choriocapillaris connects with arterial and venous channels from vessels in the outer choroidal stroma. Its function is to nourish the outer retinal layers. With age, Bruch's membrane thickens and commonly acquires focal excrescences known as drusen (Figure 13.24). Both drusen and Bruch's membrane may calcify.

Figure 13.22 Smooth muscle constitutes a large portion of the ciliary body. Pigmented melanocytes are often present in between the smooth muscle bundles (H&E, 66.)

Figure 13.23 This photomicrograph illustrates the well-vascularized choroid. At the top of the figure, the choroid abuts the sclera. The single layer of retinal pigment epithelium is present at the bottom of the figure. (H&E, 66.)

The choroidal stroma is thinnest anteriorly, near the ciliary body, where it is approximately 0.1 mm thick. Posteriorly, at the optic nerve, the choroidal stroma thickens to nearly 0.22 mm. The tenuous connection between the choroidal stroma and the sclera is responsible for both the pathologic and artifactual separations often seen between these two layers in histologic sections. The stroma contains abundant pigmented melanocytes (Figure 13.25), which are more numerous in heavily pigmented individuals than in persons with little pigment. Collagen fibers, some smooth muscle, neurons of the autonomic nervous system, and a prominent vascular system are also present. Large- and medium-sized arteries (branches of the posterior ciliary arteries) and veins (vortex veins) are situated in the outermost choroid.

Figure 13.24 An amorphous excrescence (arrow) in Bruch's membrane appears to extend into the underlying retina. Such so-called drusen are common and occasionally calcify. (H&E, 160.)

Figure 13.25 Numerous pigmented melanocytes are located within the choroidal stroma (H&E, 160.)

Retina

The cellular components of the retina include the photoreceptors (rods and cones), a variety of different neurons (ganglion, bipolar, horizontal, and amacrine cells), and neuroglial cells (M ller cells and astrocytes). Many of these special types of cells can only be detected with the aid of specific staining techniques. These constituents of the retina are stratified into several distinct layers (Figure 13.26). The rods and cones comprise the outermost part of the sensory retina and are closely apposed to the retinal pigment epithelium. The retina's anterior boundary has a serrated edge (ora serrata), at which point it is approximately 0.1 mm thick. Cysts develop in the peripheral retina (peripheral cystoid degeneration) in virtually everyone over age 20 (13) (Figures 13.27, 13.28). Here, the retina converges into a single layer of nonpigmented epithelium, which continues anteriorly to where it merges with the nonpigmented epithelium of the ciliary body (Figure 13.28). Posteriorly, the retina extends to the optic nerve, where it is approximately 0.5 to 0.6 mm thick. The sensory retina is in direct

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contact with the vitreous humor and lies interior to the retinal pigment epithelium, which defines the outermost border of the retina.

Figure 13.26 The cellular components of the retina are organized in well-defined layers. The choroid is directly above the retinal pigment epithelium (RPE) in this figure. Specialized extensions of the photoreceptors known as the outer and inner segments (OS andIS) are located immediately adjacent to the RPE. Cell bodies of the photoreceptors are present in the outer nuclear layer (ONL); synapses between the bipolar cells, horizontal cells, and the photoreceptors occur in the outer plexiform layer (OPL); the inner nuclear layer (INL) embraces nuclei of the amacrine, bipolar, horizontal, and M ller's cells; the inner plexiform (IPL) contains axons and dendrites of amacrine, bipolar, and ganglion cells; ganglion cell bodies are located in the ganglion cell layer (GCL); the nerve fiber layer (NFL) contains ganglion cell axons. (Reproduced with permission from:

Klintworth GK, Landers MB III. The Eye: Structure and Function. Baltimore: Williams & Wilkins; 1976.

)

The retinal pigment epithelium is a monolayer of cells. These epithelial cells contain numerous intracytoplasmic melanosomes; cellular processes envelope part of the overlying rods and cones as shown by transmission electron microscopy. The phagocytic function of the retinal pigment epithelium assists in the turnover of the photoreceptor elements. Undigested products of phagoliposomes culminate in the progressively increasing number of lipofuscin granules that accumulate within the retinal pigment epithelium, with time.

Some photoreceptors are cylindrical in appearance (rods), whereas others are conical-shaped and somewhat longer and thicker (cones). Internal to the photoreceptors is the outer plexiform layer, formed from cell processes of the horizontal and bipolar cells and axonal extensions of the rods and cones. The inner nuclear layer embraces the nuclei of several cell types (the bipolar, M ller, horizontal, and amacrine cells). Constituents of the inner plexiform layer include bipolar and amacrine cell axons and dendrites of the ganglion cells. Near the vitreal aspect of the retina is the ganglion cell layer, composed predominantly of ganglion cell bodies. The axons of these large neurons make up the nerve fiber layer; these processes are usually unmyelinated; but, as an incidental developmental anomaly, bundles of some nerve fibers are occasionally myelinated. In older individuals, basophilic PAS-positive intracellular rounded bodies (corpora amylacea), indistinguishable from similar structures in the brain, often accumulate in the nerve fiber layer of the retina near the optic disc. By light microscopy, two acellular zones can be distinguished within the retina: the external and internal limiting membranes. The so-called external limiting membrane is located between the photoreceptors and the outer nuclear layer. The membrane represents firm junctions between M ller cells and adjacent photoreceptors (zonula adherens). The basal lamina of the M ller cells accounts for the hyalin structure seen on light microscopy and is known as the internal limiting membrane. Similar to the neuroglial tissue of the brain, by immunohistochemistry the neuronal cells of the retina show strong immunopositivity to synaptophysin (Figure 13.29) and NeuN (Neuronal Nuclei) (14) (Figure 13.30). Neurofilament protein highlights the axons of the

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nerve fiber layer as they continue posteriorly to enter the optic nerve. Glial cells and their processes react with glial fibrillary acidic protein (GFAP) (Figure 13.31).

Figure 13.27 The ora serrata marks the anterior boundary of the retina. An almost invariable finding in the retina of all human eyes after the age of 20 is peripheral cystoid degeneration. Macroscopically, the peripheral retina immediately behind the ora serrata (arrows) has a focally vacuolated appearance (arrowhead). (Reproduced with permission from:

Klintworth GK, Landers MB III. The Eye: Structure and Function. Baltimore: Williams & Wilkins; 1976.

)

Figure 13.28 A. At the ora serrata, the multilayered retina (arrow) converges with the single layer of nonpigmented epithelium of the ciliary body (double arrows). The retina is loosely attached to the choroid (C) in the region of the ora serrata and is artifactually separated from it in this figure (H&E, 50). B. Microscopically, peripheral cystoid degeneration is characterized by the presence of numerous cystlike spaces within the retina. (Reproduced with permission from:

Klintworth GK, Landers MB III. The Eye: Structure and Function. Baltimore; Williams & Wilkins, 1976.

)

Light passes through the entire sensory retina before it is converted by the photoreceptor cells into electric impulses. The impulses are eventually transmitted to the visual cortex in the occipital lobe of the brain through a complex series of intercellular connections.

The retina varies in structure in different sites (Figure 13.32). A yellow specialized portion of the retina is located in the posterior pole of the eye (in an area slightly temporal to the optic disc). This is the macula lutea (yellow spot), where the bipolar and ganglion cells contain the pigment xanthophyll. In the macular region of the retina, the ganglion cells are several layers thick. The center of the macula contains a slightly depressed area (the fovea centralis) measuring almost 1.5 mm in diameter; it is responsible for most visual acuity. The walls of the fovea centralis are known as the clivus, and the precise center is designated the foveola. Blood vessels are absent in the foveola, which measures approximately 0.4 mm in diameter. The inner layers of the retina are displaced peripherally in the foveola so that only photoreceptors, the outer nuclear layer, and outer plexiform layer are present. Cones are located within the foveola, but rods are absent.

The microvasculature of the normal retina is composed of branches of the central retinal artery and tributaries of the central retinal vein. It contains arterioles, venules, and intervening capillaries (Figure 13.33). In capillaries from normal individuals, endothelial cells and pericytes are present in a ratio of approximately 1:1. The retinal microvasculature is affected in hypertension, diabetes mellitus, and other conditions. Capillary microaneurysms and the loss of capillary pericytes are characteristics of diabetic retinopathy. These are best visualized in flat preparations of the retina after trypsin digestion of the retinal cells.

Artifacts of the Retina

It is necessary to distinguish a true detachment of the sensory retina from the retinal pigment epithelium from an artifactitious retinal detachment in the same location. True retinal detachments are characterized by the presence of blood or eosinophilic proteinaceous fluid in the space between the two retinal layers (Figure 13.34), rounded edges at the site of the retinal break, photoreceptor elements of one fold of retina adjacent to the internal

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limiting membrane of another fold (Zimmerman's sign), an absence of photoreceptor outer segments (except in a very acute detachment), and the presence of cyst-like spaces within the detached retina. In contrast, artifactitious retinal detachments typically lack subretinal fluid that is rich in eosinophilic protein or blood, have squared-off edges at the site of the break with intact photoreceptor outer segments, and fragments of pigment epithelium cell debris are adherent to the photoreceptor outer segments (Figure 13.35) (15).

Figure 13.29 Synaptophysin immunopositivity is present within the ganglion cell layer, inner and outer nuclear layers, and inner and outer plexiform layers ( 40).

Figure 13.30 Reactivity with the immunohistochemical marker NeuN is restricted to neurons of the ganglion cell layer and a few cells in the inner nuclear layer ( 40).

Figure 13.31 Glial fibrillary acidic protein (GFAP) highlights the retinal glia and their processes ( 40).

Figure 13.32 The retina has regional histologic variations. In the macular region (left), the ganglion cells (arrow) are multilayered. In areas outside of the macula (right), ganglion cells (arrow) form a single layer. (Left, H&E, 80; right, H&E, 160.)

Figure 13.33 This flat preparation of a normal retina following trypsin digestion discloses retinal capillaries adjacent to a retinal arteriole (H&E, 25).

At the ora serrata, the sensory retina of neonates and children folds inwardly upon itself (Lange's fold) in eyes that have been subjected to a fixative such as formalin (Figure 13.36). This artifact of fixation is not observed in the living eye or in unfixed enucleated eyes that have been sectioned to observe the peripheral retina. Lange's fold is thought to result from traction on the peripheral retina by a shortening of the vitreous humor base and posterior lens zonules caused by tissue fixation. After the age of 20 years, Lange's fold is not observed, presumably because the peripheral retina has become firmly bound to the subjacent retinal pigment epithelium. The convexity of this artifact of fixation is directed anteriorly and axially in neonates; but, in older infants and children, the fold is initiated some distance from the ora serrata, apparently because of a propensity for peripheral retinal adhesions to the subjacent retinal pigment epithelium with increasing age. In contrast to a true retinal

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detachment, subretinal fluid is not present between the layers of the sensory retina in Lange's fold (16).

Figure 13.34 A feature of a true retinal detachment is the presence of eosinophilic proteinaceous fluid within the subretinal space (H&E, 20).

Figure 13.35 Artifactual retinal detachments are characterized by retinal pigment epithelium granules within the tips of the photoreceptors and the absence of subretinal eosinophilic fluid (H&E, 20).

Figure 13.36 Lange's fold is a postmortem artifact usually seen in infant eyes. At the ora serrata, the peripheral retina typically takes on a bowed or concave appearance anteriorly. The absence of subretinal fluid distinguishes this from a true retinal detachment (H&E, 10).

The Optic Nerve

More than one million axons from the retinal nerve fiber layer converge at the optic nerve head, which accounts for the physiologic blind spot in the normal visual field and represents the beginning of the optic nerve. The central retinal artery and vein traverse the optic nerve; and, within a slight depression at the origin of the nerve, they are surrounded by glial tissue (Figure 13.37). From the optic nerve head, the axons extend for approximately 1 mm to a sievelike partition of connective tissue in the sclera (the lamina cribrosa) through which the nerve fibers pass on their way to the brain. Over one thousand nerve fiber bundles surrounded by astrocytes, oligodendroglia, and collagenous septae (Figure 13.38) can be identified in cross sections of the optic nerve, which is a tract of the central nervous system. Like the brain, the optic nerve is surrounded by dura, arachnoid, and pia mater. Small focal meningothelial proliferations occasionally form within the leptomeninges surrounding the optic nerve. Some orbital meningiomas presumably arise from them. Laminated products of the meningothelial cells (psammoma bodies) sometimes occur in the arachnoid mater (Figure 13.39). Pigmented melanocytes are sometimes encountered within the leptomeninges and optic nerve head.

After leaving the globe, each optic nerve continues posteriorly through the orbit to its respective optic foramen, and then to the optic chiasm before terminating in the lateral geniculate bodies.

At the level of the lamina cribrosa, the axons within the optic nerve become myelinated by concentric membranous processes of the oligodendroglia. The rather abrupt transition between myelinated and nonmyelinated nerve fibers is eminently appreciated in tissue sections stained with Luxol fast blue or other dyes with an affinity for myelin (Figure 13.40). As the axons acquire myelin coats, the diameter of the optic nerve doubles to nearly 3 mm. Located within the central core of the optic nerve, adjacent to the globe, is the central retinal artery and vein. Both of these vascular channels exit the nerve some 8 to 15 mm posterior to the lamina cribrosa; the channels are not evident within tissue sections of the optic nerve closer to the brain. The orbital portion of the optic nerve extends some 25 mm from the lamina cribrosa to the optic foramen at the apex of the orbit. If the optic nerve becomes compressed during enucleation of the globe, some optic nerve tissue may extrude into the eye and become dislodged into the lumen of blood vessels near the optic disc, between the sensory retina and the retinal pigment epithelium, and even into the vitreous humor. Neural tissue within the optic nerve may become displaced in a manner comparable to the toothpaste artifact of the

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spinal cord that follows a traumatic insinuation of white matter into the grey matter. This artifact should not be mistaken for ectopic intraocular nervous tissue, tumors, giant drusen, vitreous humor worms, or subretinal exudates (17). With age, corpora amylacea, similar to those in the retina and brain, may become evident in the optic nerve.

Figure 13.37 The optic nerve penetrates the sclera near the posterior pole of the eye. This histologic section contains the central retinal artery (arrow) in the central part of the optic nerve. Both the central retinal artery and the central retinal vein traverse the optic nerve until they exit the nerve about 8 to 15 mm posterior to the eyeball. (Masson's trichrome, 10.)

Figure 13.38 Nerve fiber bundles within the optic nerve are surrounded by thin collagenous septae (Masson's trichrome, 50).

Figure 13.39 Laminated psammoma bodies, such as this one, are often closely associated with the meningothelial cells of optic nerve (H&E, 160).

Figure 13.40 The abrupt transition between nonmyelinated (arrow) and myelinated (double arrows) nerve fibers of the normal optic nerve at the level of the lamina cribrosa (arrowheads) is dramatically illustrated in this tissue section stained with a dye that has an affinity for myelin (Luxol fast blue, 10).

The Crystalline Lens

The biconvex ocular lens (Figure 13.41) is located directly behind the pupil and in front of the anterior face of the vitreous humor. In the adult, it measures approximately 10 mm in diameter and 4 to 5 mm in width. The lens is held in place by zonules that connect it to the pars plicata of the ciliary body. The lens is encircled by a collagen- and carbohydrate-rich capsule that serves as the site of attachment for the zonules. The capsule over the anterior surface of the lens thickens with time. At 2 to 3 years of age, the anterior capsule is almost 8 to 15 m wide and increases to 14 to 21 m by 35 years (Figure 13.42). The posterior lens capsule reaches its maximum thickness at about 35 years of age (4 23 m) and then diminishes to 2 to 9 m after age 70 years (Figure 13.43) (2). Directly interior to the anterior lens capsule is a single layer of cuboidal epithelium. These cells extend to about the level of the lens equator; they do not normally exist posterior to this point. Proliferating epithelial cells elongate at the lens equator and become displaced toward the center of the lens, known as the lens nucleus, where they are retained for life. This process continues throughout life, and the long slender cells are designated lens fibers. In the peripheral part of the lens near the equator, the fibers retain their nuclei; but, as the fibers become displaced toward the center of the lens, their nuclei disintegrate so that the center of the lens lacks nuclei. In some cataractous lenses, such as the cataract of rubella, the fibers within the center of the lens retain their nuclei.

Figure 13.41 The crystalline lens (L) is situated just posterior to the pupil and iris (arrows) (H&E, 2.5).

The normally transparent lens commonly opacifies with age. Discrete globules of degenerate lens fibers may form. They are frequently accompanied by the presence of an extension of epithelial cells posterior to the equator. The high density of the lens fibers makes it difficult to obtain histologic sections of the lens that are free from artifact.

Infant eyes can demonstrate an artifact of fixation resulting in an umbilicated, dimpled, or concave configuration of the posterior surface of the lens (18) (Figure 13.44).

Intraocular Compartments

The eye accommodates two major fluid-containing intraocular compartments. One is filled with aqueous humor, the other with vitreous humor. The aqueous humor compartment is divided into an anterior and posterior chamber (Figure 13.45). The anterior chamber is delineated in front by the cornea, peripherally by the drainage angle of the eye, and posteriorly by the pupil and the iris. The small posterior chamber is situated between the pigmented epithelia of the iris, the ciliary body, the anterior face of the vitreous humor, and the lens.

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Figure 13.42 The anterior lens capsule (arrow) appears as an eosinophilic acellular band overlying a single layer of epithelial cells in hematoxylin and eosin-stained preparations (left). The lens capsule is rich in carbohydrate and reacts intensely with the periodic acid-Schiff stain (arrow) (right). (Left, H&E, 132; right, PAS, 160.)

Figure 13.43 Posteriorly, the lens capsule (arrow) is thinner than anteriorly, and epithelial cells are absent (H&E, 132).

Figure 13.44 Infant eye demonstrating an artifact of fixation resulting in a posterior concave or umbilicated appearance of the lens. This figure also illustrates an artifactual absence of most of the corneal epithelium (H&E, 1).

The aqueous humor, a watery solution that does not normally stain with routine histologic techniques, is produced by the ciliary body and flows forward through the aperture of the pupil to the anterior chamber, where it leaves the eye through the trabecular meshwork and Schlemm's canal. The anterior chamber contains approximately 0.25 ml of aqueous humor; the posterior chamber has a volume of only approximately 0.06 ml. Normal human aqueous humor has a density slightly greater than water; and, like plasma, it contains protein, ascorbic acid, electrolytes, and glucose. The major differences between

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aqueous humor and plasma are the relatively low-protein and high-ascorbic acid concentration of aqueous humor, relative to plasma.

Figure 13.45 The anterior chamber is defined by the cornea, anterior surface of the iris, and pupil. The boundaries of the much smaller posterior chamber include the posterior surface of the iris, the ciliary body, and the anterior face of the vitreous humor. Aqueous humor is produced by the ciliary body and circulates from the posterior chamber through the pupil into the anterior chamber. Aqueous humor drains from the eye by way of the trabecular meshwork and Schlemm's canal. (Reproduced with permission from:

Klintworth GK, Landers MB III. The Eye: Structure and Function. Baltimore: Williams & Wilkins; 1976.

)

Figure 13.46 The vitreous humor (arrow) appears as an amorphous material in standard tissue sections (H&E, 50).

The vitreous humor extends from the sensory retina to the lens and contains a gel-like material composed of water, protein, hyaluronic acid, and a small population of cells, designated hyalocytes, which are rarely noted in standard tissue sections. These tissue macrophages are thought to synthesize collagen and hyaluronic acid. The gelatinous consistency of the vitreous humor is due to a framework of numerous, randomly oriented collagen fibrils. The concentration of glucose and ascorbic acid is much lower than in the aqueous humor, whereas the concentration of soluble protein is similar to that of the aqueous humor (19). The vitreous humor is attached securely to the retina at the ora serrata and near the optic disc. Occasionally, vitreous humor may be identified as an amorphous acellular material on hematoxylin and eosin-stained sections (Figure 13.46).

The Eyelids

The eyelids (Figure 13.47) can be divided into cutaneous and conjunctival portions. The cutaneous segment of the eyelid is composed of a stratified squamous epidermis overlying a loosely arranged dermis, beneath which is muscular tissue. The eyelids contain several types of skin appendages. Sebaceous glands deposit their secretions, together with decomposed whole cells, via ducts into hair follicles of the eyelashes (glands of Zeis) or into ducts that open into the lid margins (meibomian glands) (Figure 13.48). Apocrine glands, whose secretions represent the pinched-off luminal aspect of the lining acinar cells, also open into the follicles of the eyelashes (glands of Moll) (Figure 13.49). In addition, the dermis of the eyelid contains eccrine sweat glands, which discharge secretions directly onto the skin via a convoluted duct. The subcutaneous portion of the upper and lower eyelids contains concentrically arranged skeletal muscle fibers (orbicularis oculi) but very little adipose connective tissue. Striated muscle of the palpebral portion of the levator palpebrae superioris is also present in the upper eyelid; it terminates in a dense fibrocollagenous aponeurosis. Small bundles of smooth muscle fibers (M ller's muscle) are located within the upper and lower eyelids.

The junction between the cutaneous and conjunctival parts of the eyelid is demarcated clinically by a sulcus (the gray line), located between the ducts of the meibomian glands and the eyelashes. The conjunctival portion of the eyelid is made up of dense connective tissue containing the meibomian glands and the palpebral conjunctiva (Figure 13.50). The tarsus, located immediately posterior to the muscles of the eyelid, accounts for most of the rigidity of the eyelids and is covered posteriorly by conjunctival epithelium and a thin subepithelial stroma. As described earlier, accessory lacrimal glands are present in the palpebral conjunctiva.

The presence of more prominent subcutaneous, suborbicularis, and pretarsal fat tissue in the upper eyelid (the pretarsal fat pad) distinguishes an Asian eyelid from a Caucasian eyelid (20).

The Orbit

The posterior and peripheral borders of the orbit are defined by bones of the skull, face, and nose. At the anterior orbital margin, the periosteum of the orbital bones gives rise to a dense connective tissue sheet (the orbital septum) (Figure 13.47A), which extends forward to insert into the eyelids. Tissue posterior to this septum is considered to be within the orbit. In the human adult, the orbit measures approximately 40 mm in height, 45 mm in depth, and has a volume of almost 30 mL. Several bony canals allow for transmission of blood vessels and nerves into and out of the orbit, posteriorly. The contents of the orbit are organized in a complex three-dimensional arrangement (Figure 13.51). Aside from the eye, the optic nerve and its meningeal coverings, Tenon's capsule, the extraocular muscles, the lacrimal gland, blood vessels, and a delicate framework of fibroadipose connective tissue constitute the major components of the orbit.

The only epithelial structure normally present in the orbit is the lacrimal gland (Figure 13.52). Closely apposed to the globe and situated in the superolateral aspect of the orbit, this gland is traditionally divided into two parts: a larger orbital lobe and a smaller palpebral lobe. About a dozen ducts from the lacrimal gland open into the superior conjunctival fornices and transmit their secretions into the tear film. The lacrimal gland is not encapsulated, and thin fibroconnective tissue septae divide the tissue into lobules

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composed of acini and lined by columnar-shaped cells. Occasionally, some lobules extend posteriorly behind the globe. Most cells are serous in type and contain scattered intracytoplasmic fat droplets and granules. Mucinous cells similar to those of salivary glands are not usually present in the acini but may be identified in the ducts. In addition to secretory cells, the lining of the larger peripheral ducts within the lacrimal gland contain myoepithelial cells external to the serous cells. Occasional lymphocytes and plasma cells are commonly present between the acini of the lacrimal gland.

Figure 13.47 A. Components of the eyelid as illustrated on this drawing include skin and cutaneous appendages, muscle, connective tissue, and conjunctiva. (Reproduced with permission from

FW Newell. Ophthalmology: Principles and Concepts. 6th ed. St. Louis: CV Mosby; 1986.

) B. The skin surface (S), the orbicularis oculi muscle (OO), the tarsus (T), and the conjunctiva (C) are evident in this histologic section of an eyelid (H&E, 3.3). C. Multiple foci of accessory lacrimal gland tissue (glands of Krause and Wolfring) are present in the eyelids. (Reproduced with permission from:

Newell FW. Ophthalmology: Principles and Concepts. 6th ed. St. Louis: CV Mosby; 1986.

)

Figure 13.48 Modified sebaceous glands, the meibomian glands, deposit secretions into ducts that open onto the eyelids. A valve is evident (arrow) in this duct of a meibomian gland. (H&E, 33.)

Figure 13.49 Apocrine glands (glands of Moll) (arrows) occur in the eyelid and open into the follicles of the eyelashes (H&E, 33).

Figure 13.50 The tarsus, composed of dense fibrous tissue, contains the meibomian glands (arrow). The palpebral conjunctiva is immediately beneath the tarsus at the bottom of this figure. (H&E, 13.2.)

Figure 13.51 The bony cavity of the orbit contains the eyeball and its fibrous covering (Tenon's capsule), the cartilagenous trochlea, the lacrimal gland, and the extraocular muscles. The trochlea and the lacrimal gland are located within the superonasal and superotemporal aspects of the orbit respectively. Some of the extraocular muscles originate from a ring of fibrous tissue in the posterior orbit known as the annulus of Zinn. (Reproduced with permission from:

Tasman W, Jaeger EA, eds. Duane's Clinical Ophthalmology. Vol. 2. Philadelphia: JB Lippincott; 1989.

)

Figure 13.52 Acini of the lacrimal gland are lined by columnar-shaped epithelial cells. Scattered lymphocytes and plasma cells are normally present in the gland. (H&E, 80.)

The orbit contains the cranial nerves, which innervate the extrinsic muscles of the eye (oculomotor, trochlear, and abducens nerves) and branches of the ophthalmic division of the trigeminal nerve, as well as parasympathetic and sympathetic nerves that innervate the cornea, conjunctiva, and the muscles of the ciliary body and iris. Neurons of the ciliary ganglion, which is located near the optic nerve close to the orbital apex and which measures approximately 2 mm in diameter, receive parasympathetic and sympathetic nerve fibers.

Other constituents of the orbit include smooth muscle (Figure 13.53) (21) and the arc-shaped structure (trochlea), through which the tendon of the superior oblique muscle passes before insertion upon the eyeball (Figure 13.54). The trochlea is the only cartilaginous structure normally present in the orbit. It arises from the superior nasal aspect of the frontal bone.

Lymphatic channels do not exist in the orbit according to traditional teaching; but this point is disputed because lymphangiomas develop in the orbit on rare occasions (22). The orbit normally lacks lymphoid tissue but contains scattered lymphocytes. These cells presumably give rise to the monoclonal and polyclonal lymphoid proliferations that frequently develop within the orbit, creating diagnostic and prognostic difficulty for the pathologist (23).

Figure 13.53 Smooth muscle bundles (arrows) are present in the soft tissues of the orbit (H&E, 10).

Figure 13.54 The arc-shaped trochlea (arrow), the only cartilaginous structure of the normal orbit, envelops the skeletal muscle fibers of the superior oblique muscle (SOM) (H&E, 5).

Lacrimal Drainage Apparatus

The lacrimal drainage apparatus (Figure 13.55), composed of the puncta, canaliculi, lacrimal sac, and the nasolacrimal duct, collects the tears and drains them to the nose. Tear fluid drains toward the medial canthus and then passes through an opening in the medial aspect of each eyelid, known as the lacrimal punctum. The puncta drain into the lacrimal canaliculi, tubular structures approximately 0.5 mm in diameter. Initially, The canaliculi are oriented vertically but, within 2 mm of their origin, bend at right angles to become almost horizontal within the eyelids. The distal portions of the canaliculi exit the

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upper and lower eyelids. They merge to form the lacrimal sac, which is encased by bones located in the inferomedial wall of the orbit. A duct (the nasolacrimal duct) that is nearly 1 cm long drains the lacrimal sac into the inferior nasal meatus of the nose. The epithelium lining the lacrimal drainage apparatus varies in different regions. In the canaliculi, it is a nonkeratinizing stratified squamous epithelium (Figure 13.56), but in the lacrimal sac and duct, the epithelium is stratified columnar in type and contains mucus-secreting goblet cells surrounded by connective tissue (Figure 13.57).

Figure 13.55 The lacrimal gland and drainage apparatus are illustrated here. The lacrimal gland is located in the superotemporal aspect of the orbit and contributes secretions to the tear film. Tears enter the canaliculi through the puncta and drain through the nasolacrimal sac and duct to eventually reach the inferior meatus within the nose.

Figure 13.56 The lacrimal canaliculi are lined by nonkeratinizing stratified squamous epithelium and are surrounded by fibrous tissue (H&E, 13.2).

Figure 13.57 The epithelium of the lacrimal sacs and ducts is stratified columnar and contains goblet cells (H&E, 50).

Acknowledgment

The authors acknowledge the contribution of Mark W. Scroggs to previous editions of this chapter.

References

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Histology for Pathologists
Histology for Pathologists
ISBN: 0781762413
EAN: 2147483647
Year: 2004
Pages: 53

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