Uvea

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Chapter 3 Uvea

The middle layer of the eye, the uvea (uveal tract), is composed of three regions (from front to back): the iris, ciliary body, and choroid. The uvea sometimes is called the vascular layer because its largest structure, the choroid, is composed mainly of blood vessels, which supply the outer retinal layers.

Iris

The iris is a thin, circular structure located anterior to the lens, often compared with a diaphragm of an optical system. The center aperture, the pupil, actually is located slightly nasal and inferior to the iris center.1 Pupil size regulates retinal illumination. The diameter can vary from 1 mm to 9 mm depending on lighting conditions. The pupil is very small (miotic) in brightly lit conditions and fairly large (mydriatic) in dim illumination. The average diameter of the iris is 12 mm, and its thickness varies. It is thickest in the region of the collarette, a circular ridge approximately 1.5 mm from the pupillary margin. This slightly raised jagged ridge was the attachment site for the fetal pupillary membrane during embryologic development.1,2 The collarette divides the iris into the pupillary zone, which encircles the pupil, and the ciliary zone, which extends from the collarette to the iris root (Figure 3-1). The color of these two zones often differs.

The pupillary margin of the iris rests on the anterior surface of the lens and, in profile, the iris has a truncated cone shape such that the pupillary margin lies anterior to its peripheral termination, the iris root (Figure 3-2). The root, approximately 0.5 mm thick, is the thinnest part of the iris and joins the iris to the anterior aspect of the ciliary body (Figure 3-3).1 The iris divides the anterior segment of the globe into anterior and posterior chambers, and the pupil allows the aqueous humor to flow from the posterior into the anterior chamber with no resistance.

Histologic Features of Iris

The iris can be divided into four layers: (1) the anterior border layer, (2) stroma and sphincter muscle, (3) anterior epithelium and dilator muscle, and (4) posterior epithelium.

Anterior Border Layer

The surface layer of the iris, the anterior border layer, is a thin condensation of the stroma. In fact, some do not consider this to be a separate layer. It is composed of fibroblasts and pigmented melanocytes. The highly branching processes of the cells interweave to form a meshwork in which the fibroblasts are on the surface and the melanocytes are located below1,2 (Figure 3-4). The thickness of the melanocyte layer may vary throughout the iris, with accumulations of melanocytes forming elevated frecklelike masses, evident in the anterior border layer. The density and arrangement of the meshwork differ among irises and are contributing factors in iris color.

The anterior border layer is absent at the oval-shaped iris crypts. Near the root, extensions of this layer form finger-shaped iris processes that can attach to the trabecular meshwork. The number of these processes varies, but they usually do not impede aqueous outflow. The anterior border layer ends at the root.

Iris Stroma and Sphincter Muscle

The connective tissue stroma is composed of pigmented and nonpigmented cells, collagen fibrils, and extensive ground substance. The pigmented cells include melanocytes and clump cells, whereas the nonpigmented cells are fibroblasts, lymphocytes, macrophages, and mast cells.1 Although melanocytes and fibroblasts have many branching processes, the cells are widely spaced in the stroma, so their branches do not form a meshwork. Clump cells are large, round, darkly pigmented cells and are likely “altered macrophages” and are scavengers of free pigment within the iris.1,3 Clump cells usually are located in the pupillary portion of the stroma, often near the sphincter muscle (Figure 3-5). The collagen fibrils are arranged in radial columns (trabeculae) that are seen easily as white fibers in light-colored irises.3

The iris arteries are branches of a circular vessel, the major circle of the iris, located in the ciliary body near the iris root. The iris vessels usually follow a radial course from the iris root to the pupil margin. These vessels were historically thought to have an especially thick tunica adventitia and have been called “thick-walled blood vessels.”13 Improved histologic staining has shown, however, that the bundles of collagen fibrils encircling the vessels are continuous with the collagen network of the stroma and not part of the actual vessel wall. This fibril network anchors the vessels in place and protects them from kinking and compression during the extensive iris movement that occurs with miosis and mydriasis.4 An incomplete circular vessel, the minor circle of the iris, is located in the iris stroma inferior to the collarette and is a remnant of embryologic development. The iris capillaries are not fenestrated and form part of the blood-aqueous barrier.1 The iris stroma is continuous with the stroma of the ciliary body.

The sphincter muscle lies within the stroma (see Figure 3-5) and is composed of smooth-muscle cells joined by tight junctions.1 As its name implies, the sphincter is a circular muscle 0.75 to 1 mm wide, encircling the pupil and located in the pupillary zone of the stroma1,2 (Figure 3-6). The sphincter muscle is anchored firmly to adjacent stroma and retains its function even if severed radially.1 Contraction of the sphincter causes the pupil to constrict in miosis. The muscle is innervated by the parasympathetic system.

Anterior Epithelium and Dilator Muscle

Posterior to the stroma are two layers of epithelium. The first of these, the epithelial layer lying nearest to the stroma, is the anterior iris epithelium, which is composed of the unique myoepithelial cell. The apical portion is pigmented cuboidal epithelium joined by tight junctions and desmosomes, whereas the basal portion is composed of elongated, contractile, smooth muscle processes (Figure 3-7). The muscle fibers extend into the stroma, forming three to five layers of dilator muscle fibers joined by tight junctions (Figure 3-8).

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FIGURE 3-7 Posterior epithelial layers.

Anterior iris epithelium has two morphologically distinct portions: apical epithelial portion (a) and basal muscular portion (b). Cytoplasm of basal portion is filled with myofibrils and moderate number of mitochondria. Tonguelike muscular processes overlap, creating three to five layers. Tight junctions (arrows), such as those in sphincter muscle, are found between dilator muscle cells. A basement membrane (c) surrounds the muscle processes. Unmyelinated nerves and associated Schwann cells (d), as well as a few naked axons, innervate sphincter muscle. Axon (e) is in close contact with anterior epithelium, separated from it by a space measuring 200 Å wide. Cytoplasm of epithelial portions contains cell organelles, melanin granules, nucleus, and bundles of myofilaments. Most intercellular junctions present here are macula occludens, and only a few desmosomes are present; desmosomes are not found in muscular portion. Apical surface of anterior epithelium is contiguous with that of posterior epithelium. Desmosomes and tight junctions join the two layers, but some areas of separation (f) exist between the cells. The spaces so formed are filled with microvilli, and an occasional cilium also is found here (double arrows). Posterior pigmented iris epithelium shows lateral interdigitations (g) and areas of infolding along its basal surface (h). A typical basement membrane (i) is found on the basal side as well. Numerous tight junctions and desmosomes occur along lateral and apical walls. Cytoplasm of this epithelium contains numerous melanin granules, measuring approximately 0.8 mm in cross section and up to 2.5 mm in length. Stacks of cisternae of rough-surfaced endoplasmic reticulum, clustered unattached ribosomes, mitochondria, and a Golgi apparatus are typically observed.

(From Hogan MJ, Alvarado JA, Weddell JE: Histology of the human eye, Philadelphia, 1971, Saunders.)

The dilator muscle is present from the iris root to a point in the stroma below the midpoint of the sphincter.1 The stroma separating the sphincter and dilator muscles is a particularly dense band of connective tissue. Near the termination of the dilator muscle, small projections insert into the stroma or, more accurately, into the sphincter1,2 (see Figure 3-6). Because the fibers are arranged radially, contraction of the dilator muscle pulls the pupillary portion toward the root, thereby enlarging the pupil in mydriasis. The dilator is sympathetically innervated.

The anterior iris epithelium continues to the pupillary margin as cuboidal epithelial cells, and the anterior iris epithelium continues posteriorly as the pigmented epithelium of the ciliary body.

Posterior Epithelium

The second epithelial layer posterior to the stroma is the posterior iris epithelium, a single layer of heavily pigmented, approximately columnar cells joined by tight junctions and desmosomes.2,3 In the periphery, the posterior iris epithelium begins to lose its pigment as it continues into the ciliary body as the nonpigmented epithelium. A thin basement membrane covers the basal aspect of this cellular layer, which lines the posterior chamber.

The anterior and posterior iris epithelial layers are positioned apex to apex, a result of events during embryologic development. Apical microvilli extend from both surfaces, and desmosomes join the two apical surfaces. The epithelial cells curl around from the posterior iris to the anterior surface at the pupillary margin, forming the pigmented pupillary ruff (or frill), which encircles the pupil; this normally has a serrated appearance (see Figure 3-6).

Clinical Comment: Iris Synechiae

IRIS SYNECHIA is an abnormal attachment between the iris surface and another structure. In a posterior synechia, the posterior iris surface is adherent to the anterior lens surface. In an anterior synechia, the anterior iris surface is adherent to the corneal endothelium or the trabecular meshwork. Synechiae can occur as a result of a sharp blow to the head or a whiplash-type movement that brings the two structures forcefully together. Alternatively, cells and debris from a uveal infection that are circulating in the aqueous humor can make the surfaces “sticky” and so cause synechiae.5

If a posterior synechia involves a large portion of the pupillary margin, aqueous will accumulate in the posterior chamber. Continual production of aqueous causes the pressure in the posterior chamber to increase, which in turn causes the iris to bow forward in a configuration called iris bombé. This can push the peripheral iris against the trabecular meshwork, setting the stage for a dramatic increase of intraocular pressure (IOP). A drug-induced dilation usually will break a posterior synechia. The break usually occurs between the epithelial layers, leaving remnants of the posterior epithelium on the anterior surface of the lens.

An anterior synechia usually occurs at the iris periphery and involves the meshwork. It is called a peripheral anterior synechia (PAS). Aqueous outflow is impeded by a PAS, causing an increase in IOP if the adhesion occupies a considerable amount of the trabecular meshwork.

Anterior Iris Surface

Thin, radial, collagenous columns or trabeculae are evident in lightly pigmented irises. Thicker, radially oriented, branching trabeculae encircle depressions or openings in the surface called crypts.3 Crypts are located on both sides of the collarette (Fuchs’ crypts) and near the root (peripheral crypts). They allow the aqueous quick exit and entrance into spaces in the iris stroma as the volume of the iris changes with iris dilation and contraction.

Circular contraction folds, evident on the anterior surface of the ciliary zone, result from tissue moving toward the iris root during pupillary dilation. Figure 3-9 shows the topography of the anterior and posterior iris surfaces.

Iris Color

It was once thought that iris color depended on the arrangement and density of connective tissue components in the anterior border layer and stroma, the number of melanocytes, and the size and density of melanin granules within the melanocytes.6 Studies in which melanocyte counts have been done between irises of various colors and from different races have shown that the number of melanocytes is fairly constant.7,8 Color seems to be determined by the number of melanin granules within the melanocytes and the area they occupy.6 The type of melanin present and the arrangement of the connective tissue components can also affect the transmission and reflection of light contributing to iris color.9 An iris appears blue for the same reason that the sky is blue; the wavelength seen results from light scatter caused by the arrangement and density of the connective tissue components. Other iris colors are caused by the amount of light absorption, which depends on the pigment density within the melanocytes. If the iris is heavily pigmented, the anterior surface appears brown and smooth, even velvety, whereas in a lighter iris, the collagen trabeculae are evident and the color ranges from grays to blues to greens depending on the density of pigment and collagen. A freckle or a nevus is an area of hyperpigmentation, an accumulation of melanocytes, and frequently is seen in the anterior border layer. In all colored irises, the two epithelial layers are heavily pigmented. Only in the albino iris do the epithelial layers lack pigment.3

Ciliary Body

When viewed from the front of the eye, the ciliary body is a ring-shaped structure. Its width is approximately 5.9 mm on the nasal side and 6.7 mm on the temporal side.2 The posterior area of the ciliary body, which terminates at the ora serrata, appears fairly flat, but the anterior ciliary body contains numerous folds or processes that extend into the posterior chamber. In sagittal section, the ciliary body has a triangular shape, the base of which is located anteriorly; one corner of the base lies at the scleral spur, the iris root extends from the approximate center of the base, and portions of the base border both the anterior and posterior chambers. The outer side of the triangle lies against the sclera, and the inner side lines the posterior chamber and a small portion of the vitreous cavity (Figure 3-11). The apex is located at the ora serrata.

The ciliary body can be divided into two parts: the pars plicata (corona ciliaris) and the pars plana (orbicularis ciliaris). The pars plicata is the wider, anterior portion containing the ciliary processes (see Figure 3-10). Approximately 70 to 80 ciliary processes extend into the posterior chamber, and the regions between them are called valleys of Kuhnt. A ciliary process measures approximately 2 mm in length, 0.5 mm in width, and 1 mm in height, but there are significant variations in all measurements.1

The pars plana is the flatter region of the ciliary body. It extends from the posterior of the pars plicata to the ora serrata, which is the transition between ciliary body and choroid. The ora serrata has a serrated pattern, the forward-pointing apices of which are called teeth or dentate processes. The rounded portions that lie between the teeth are called oral bays (Figure 3-12, A). The dentate processes are elongations of retinal tissue into the region of the pars plana.