the ora serrata to the root of the iris. It is divided into two main zones: posterior, the smooth pars plana (orbiculus ciliaris), and anterior, the pars plicata (corona ciliaris). It is triangular in horizontal section and is coated by a double layer of the ciliary epithelium. The outer layer of epithelium is amelanotic and is in contact with the vitreous body. The inner layer of epithelium is amelanotic until it reaches the iris and then is highly pigmented, continuous with the retinal pigment epithelium (RPE), and covers the cells of the dilator muscle. The retina ends at the ora serrata portion of the ciliary body, the function of which is to secrete the aqueous humor. There are three sets of ciliary muscles in the eye: the longitudinal, radial, and circular muscles. They are near the front of the eye, above and below the lens. They are attached to the lens by connective tissue called the zonules of Zinn and are responsible for shaping the lens to focus light on the retina. The ciliary body has four functions: accommodation, aqueous humor production, restoration of vitreous mucopolysaccharide, and the production and maintenance of the lens zonules. One of the most essential roles of the ciliary body is the production of the aqueous humor, which is responsible for providing most of the nutrients for the lens and the cornea as well as waste management of these areas.

Nutrients for the ciliary body come from the same blood vessels that supply the iris. Those vessels in the anterior ciliary body also supply blood to the limbal tissues, anterior choroid, and the ciliary body. The main arterial supply to the ciliary body is through the long posterior and the anterior ciliary arteries, which come together to form the major arterial circle of the iris just posterior to the anterior chamber angle recess (Fig. 1.2). From the MAC, branches pass to the anterior part of the ciliary processes, where they form a capillary bed. Branches also go to the stroma and ciliary muscle, and others pass to the iris, anterior limbal region, and anterior choroid. The capillaries of the ciliary processes are large and fenestrated rather like the choriocapillaris. The capillaries in the ciliary muscle are smaller and less fenestrated. The principal route of venous drainage is posteriorly into the choroid and vortex

vein system and, to a lesser extent, into the intrascleral venous plexus and episcleral veins in the limbal region.

The ciliary body is difficult to study in vivo because of its location in the eye; a small amount of its anterior surface can be seen indistinctly with the gonioscope, while the pars plana and ora serrata can be seen with the indirect ophthalmoscope and with the three-prism contact lens of Goldmann when the sclera is depressed.

The ciliary body is a main target of drugs against glaucoma, as the ciliary body is responsible for aqueous humor production; lowering aqueous humor production will cause a subsequent drop in the intraocular pressure.

With age, everyone develops a condition known as presbyopia. This occurs as the ciliary body muscle and lens gradually lose elasticity, causing difficulty in reading.

1.2.3Choroid and Suprachoroid

The choroid’s anterior boundary is Bruch’s membrane, which separates retina from choroid, and the posterior boundary is the lamina fusca, which is a transition zone composed of layers of long, collagenous, ribbonlike processes that branch and are interconnected and separate choroid from sclera. The choroid is a long, thin, vascular, and pigmented tissue, which forms the posterior portion of the uveal tract (the iris, ciliary body, and choroid). Because of its great vascularity, the choroid has some of the properties of erectile tissue. The choroidal vessels supply blood to and receive blood from the anterior portion of the eye as well as nourish the outer retina and carry waste from the RPE. The choroidal vasculature in primates is composed of the choriocapillaris (an internal or anterior layer), medium-sized vessels (Sattler’s layer) measuring 40–90 mm, and large arteries and veins measuring 20–100 mm are posterior (Haller’s layer). Its capillaries form a very unusual pattern (Fig. 1.7), being arranged in a single layer restricted to the inner portion of the choroid; this arrangement enables the capillary layer to provide nutrition for the outer retina.

1.2.3.1Development of the Choroidal Vasculature

The choroid is derived embryonically from mesoderm, neural crest cells, and neuroectoderm. The condensation of neural crest cells that occurs initially around the anterior region of the optic cup and proceeds posteriorly to the optic stalk differentiates into the cells of the ensheathing choroidal stroma [19]. Endothelium-lined blood spaces appear very early in the mesenchymal tissue and first coalesce anteriorly at the rim of the optic cup to form the embryonic annular vessel. Prior to the fourth week (5.0-mm embryonic stage), the associated mesoderm surrounding the optic cup is undifferentiated.

We have recently demonstrated that the initial human choriocapillaris develops by hemovasculogenesis: differentiation of endothelial, hematopoietic, and erythropoietic cells from a common precursor, the hemangioblast [14]. At 6–7 WG, erythroblasts [nucleated erythrocytes expressing epsilon hemoglobin (Hbe)] were observed within the islands of precursor cells (blood-island-like formations) in the choriocapillaris layer and scattered within the forming choroidal stroma. Often, the same Hbe+ cells coexpressed endothelial cell (CD31, CD39), hematopoietic (CD34), and angioblast markers (VEGFR-2) suggesting that they had a common progenitor, the hemangioblast. By 8–12 WG, most of the erythroblasts had disappeared, and vascular lumen became apparent in choriocapillaris. Uniquely, the capillaries (choriocapillaris) form first without any association with intermediate or large vessels.

Rudimentary vortex veins appear in the upper and lower nasal and temporal quadrants of the eye during the sixth week [19]. The short posterior ciliary arteries also appear in the mesoderm choroidal condensation. By the 11th WG (50to 60-mm stage), these arteries have branched extensively throughout the choroid. At 14–23 WG, some endothelial cells were proliferating on the scleral side of choriocapillaris in association with forming deeper vessels, suggesting that angiogenesis is responsible for the apparent anastomosis between the choriocapillaris and intermediate blood vessels.

1.2.3.2 Arteries

There are three main arterial sources of blood to the choroid: long posterior ciliary arteries (LPCAs, temporal, and nasal), short posterior ciliary arteries (SPCAs), and the anterior ciliary artery. The LPCAs follow long, oblique intrascleral courses traveling in the potential suprachoroidal space and send branches from the ora serrata region posteriorly to supply the choroid as far posterior as the equator (Fig. 1.7). A ciliary nerve accompanies each LPCA. There are 15–20 SPCAs in man that supply the choroid from equator to optic nerve (Fig. 1.7) while there are no SPCAs in rodents (Fig. 1.8). The arteries surround the optic nerve (the circle of Zinn) in the posterior pole, penetrating and then branching peripherally in a wheel-shaped arrangement (Fig. 1.3). Triangular watersheds separate the radial areas supplied by the arteries with the apices directed toward the fovea, which is

Fig. 1.8 Cast of an entire rat choroidal vasculature viewed from the scleral aspect. Two long ciliary arteries (asterisks) originate from the optic nerve and traverse temporally and nasally. There are no SPCAs in rodent, only branches of the two LPCAs. The vortex veins are marked with arrows (temporal is left and nasal is right) (From Bhutto [4], Anat Rec, p. 654)

the anatomic basis of the triangular syndrome. A watershed zone in choroid is an area that normally fills and drains slowly with blood that occurs in areas supplied by two or more end arteries. Hayreh, after extensive in vivo experimental studies on choroidal circulation and its watershed zones in monkey and man, argues that the choroidal vascular bed is a strictly segmental and end-arterial system and has watershed zones situated between the various PCAs, the short PCAs, the choroidal arteries, the arterioles, and the vortex veins [17]. There is great variability in humans on the location of watershed zones of choroid, but their significance is that a fall in perfusion pressure in one or more of the arteries in the involved area can result in ischemia due to the poor vascularity of the watershed zone [17]. The nature of the choroidal vasculature and the existence of watershed zones in the choroid are controversial, of great clinical importance, and probably play a significant role in the production of various ischemic lesions in the choroid.

The final arterial source of blood to choroid is the anterior ciliary arteries, which send recurrent branches posteriorly to supply the choroid

Fig. 1.9 Schematic of the blood vessels of the uveal tract in human. One of the two LPCAs (A) is present traveling along the horizontal meridian. It bifurcates at the ora serrata and immediately branches into arteries that traverse back (arrows) to supply the anterior choriocapillaris including the equator. The SPCAs enter the choroids near the optic nerve (c) and then divide quickly to supply the posterior choriocapillaris (not shown). The ACA (D) enters the globe through the rectus muscle and traverse through the sclera into the ciliary body. The ACA yields 8–12 branches (e) before joining the major circle of iris (f). The major circle of the iris branches anteriorly into the iris (g) and posteriorly into the ciliary body. The circle of Zinn (h) lies in the sclera and supplies some of the blood to the optic nerve and disk. The vortex veins form an ampulla (k) before exiting the globe through the sclera (J). The vortex veins not only drain an entire quadrant of the choroid but also drain blood from the iris and ciliary body. Some anterior veins, however, enter the episcleral system of veins (From Hogan [19], p. 326, with permission)

at 3 o’clock and 9 o’clock soon after they pierce the anterior sclera. At the major iridal circle, anastomoses are found between short, long, and anterior ciliary arteries and the arteries of all three-vessel systems rapidly extend internally via arterioles to supply blood to the choriocapillaris (Fig. 1.3). Mast cells are intimately associated with most choroidal arteries and may provide cytokines, proteolytic enzymes, and potent vasomodulatory substances for these arteries.

1.2.3.3 Choroidal Veins (Vortex Veins)

The main venous drainage of the choroid occurs through four to six vortex veins located at the equator (Fig. 1.9) that drain into superior and

inferior ophthalmic veins. In the submacular area, the venous portion predominates over the arterial portion, and venules are closely arranged. The meshwork of the venous plexus becomes less dense with increasing distance from the macula. The vessels are straighter in the extramacular region, losing the tortuosity that is characteristic of the macular region. Vessels of larger lumen form the subcapillaris plexus and eventually flow into the vortex veins (Fig. 1.9). Venous drainage is segmentally organized into quadrants, with watersheds oriented horizontally through the disk and fovea and vertically through the papillomacular region. Arterial and venous choroidal watersheds are under the center of the macula, which may either predispose it to relative ischemia or prevent ischemia through multiple submacular blood supplies.

1.2.3.4 Choriocapillaris

The choriocapillaris, located solely in the internal portion of the choroid, appears as a nonhomogenous network of large (10–38 mm) capillaries [35]. Modern histological and image analysis techniques suggest much smaller diameters for choriocapillaris [34]; for example, using the alkaline phosphatase flat embedded choroid technique [26], we find submacular capillaries to be an average diameter of 14.7 mm (McLeod and Lutty, unpublished results; [26]). This monolayer vascular network, flattened in the anterior-posterior aspect, changes from a dense, honeycomb-like, nonlobular structure in the peripapillary area to a lobule-like pattern in submacular areas and most of the posterior pole and equatorial areas (Fig. 1.10). The choriocapillaris lobules measure 0.6–1.0 mm. In the peripheral area, the pattern of choriocapillaris is a more elongated, palmlike, or fanlike vascular network forming arcades that terminate at the ora serrata [26]. The network of choriocapillaris is supplied by feeding arterioles derived from the short posterior ciliary arteries and drained by the collecting venules (Fig. 1.10). These arterioles and venules form the medium-sized vessels of the choroid occupying the choroidal stroma (Sattler’s layer). The majority of these vessels in the peripapillary

Fig. 1.10 Pattern of choriocapillaris in the posterior pole (a), equator (b), and periphery (c) in a flat mount human choroids incubated for alkaline phosphatase (APase) activity and then bleached. Venous blood vessels and capillaries have the most intense APase activity, while arterial blood vessels have the least. The lobular pattern is apparent in the pole (a) and at the equator (b), while the capillaries are more ladderlike in the periphery (c)

and submacular areas form a 90° angle with the posterior aspect of the choriocapillaris.

There is controversial evidence that both supports and disproves the idea that “lobules” exist and subdivide the choroid into many functional islands. Wybar [46], in his studies of human eyes,