but not horizontal rectus muscles (the vertical meridian of the anterior uvea is insufÞciently perfused by the long posterior ciliary artery) [28, 29]. Other studies suggest that the anterior episcleral circulation is supplied by retrograde or centrifugal ßow in the perforating ciliary arteries derived from the long posterior ciliary arteries [31, 32, 34, 42, 43]. Some investigators have argued that this retrograde ßow represents emissary veins that drain the deep circulations of the anterior uvea into the superÞcial episcleral venous system [21, 30, 44]. Others believe that it results from deÞciencies in photographic and conventional video camera techniques [35]. The resolution of this controversy will require further studies.

1.3.1.4 Nerve Supply

The posterior ciliary nerves perforate the sclera around the optic nerve. The many short posterior ciliary nerves supply the posterior region of the sclera, whereas the two long posterior ciliary nerves supply the anterior portion. Because the sclera receives a profuse sensory innervation, scleral inßammation may cause severe pain. In addition, because the extraocular muscles have their insertions in the sclera, the pain may increase with ocular movement.

A branch of the long posterior ciliary nerve (intrascleral nerve loop of Axenfeld) may loop out through the sclera in the region of the ciliary body, forming a clinically visible nodular elevation 4Ð7 mm posterior to the limbus. These nerve loops are found in 12% of the eyes as a normal anatomic variation and are usually associated with blood vessels. It is sometimes of clinical signiÞcance because the nerves are occasionally accompanied by pigmented chromatophores, which may produce a pigmented spot on the sclera. They can be slightly painful if they lie in the episclera. Because such a nerve loop may be mistaken for a melanotic tumor or for a foreign body, it must be included in the differential diagnosis of primary or metastatic malignant melanoma occurring in this region [45]. They obviously should not be removed.

Fig. 1.19 Transmission electron micrograph of adult human sclera (×11,000). Note the Þbroblast, the collagen bundles, both longitudinal and transverse, with variable-diameter Þbrils forming bundles more irregularly arranged than is seen in the cornea

1.3.2Ultramicroscopic Anatomy

1.3.2.1 Sclera

The sclera is composed of dense bundles of collagen, few elastic Þbers, few Þbroblasts, and a moderate amount of amorphous ground substance (proteoglycans and glycoproteins) (Fig. 1.19).

Collagen bundles consist of long, branched Þbrils with a macroperiodicity of about 64 nm (range, 35Ð75 nm) and a microperiodicity of 11 nm. Unlike the uniform corneal collagen, the collagen Þbrils in sclera vary in diameter, ranging from 28 to 300 nm, and their arrangement in the individual bundles is more random than in the cornea [46Ð49]. Collagen bundles in sclera vary in diameter ranging from 0.5 to 6.0 mm and form complex and irregular branching patterns, curving around the muscular insertions and the optic nerve (Figs. 1.20 and 1.21). Collagen bundles in the outer region are thinner (0.5Ð2 mm) than those

Fig. 1.20 Transmission electron micrograph of human sclera (×26,000). Transverse section of collagen bundles in the sclera. The macroperiodicity is approximately 64 nm

Fig. 1.21 Transmission electron micrograph of adult sclera (×26,000). Note the periodicity in the longitudinal Þbers and the variable Þbril diameter in the transverse bundles

in the inner region; they usually run in a lamellar fashion, whereas those in the inner region are interwoven randomly, forming irregular and intermingled arrangements [49, 50]. These arrangements may account for the rigidity and ßexibility against changes in intraocular pressure and for the opacity of the sclera.

The Þbrils at the emissary canals run parallel to the direction of the canal. Few of these Þbrils attach to the wall of the vessel or nerve in the canal. A small number of Þne elastic Þbers (10Ð 12 nm in diameter) lie parallel to the collagen Þbrils [49, 51].

Flat stellate or spindle-shaped cells, the Þbroblasts, are few in number along the bundles of collagen (Fig. 1.22). The long axis of the cell (and the large elliptical nucleus) is parallel to the surface [37]. The nucleus has one or two nucleoli and the chromatin is sparse. Quiescent Þbroblasts contain a relative scanty cytoplasm with long mitochondria, a small Golgi complex, a few cisternal proÞles of granular endoplasmic reticulum, and occasional small fat droplets. During growth or repair, however, the Golgi complex and the granular endoplasmic reticulum become prominent. The Þbroblast elaborates the precursors of the amorphous ground substance components as well as the Þbrillar proteins, such as collagen and elastin. Following secretion, the Þbrils lie on the cell surface while full maturation into Þbers occurs.

The amorphous ground substance, composed of proteoglycans and glycoproteins, Þlls intercellular and interÞbrillar spaces. Proteoglycans, demonstrated by cuprolinic blue stain, are Þne Þlaments, approximately 54 nm in length and 5 nm in diameter; they are localized around, along, and radiating from the collagen Þbrils [52].

1.3.2.2 Vessels

Our own transmission electron microscopy studies on human adult sclera showed that episcleral vessels, as capillaries and postcapillary venules, are continuous and had simple walls consisting of endothelial cells attached to an underlying basement membrane secreted by them and a discontinuous layer of pericytes (Figs. 1.23Ð1.25).

Fig. 1.22 Transmission electron micrograph of human adult sclera (×17,750). Note the ßat, spindle-shaped cells with long nuclei containing marginated chromatin. These Þbroblasts are in a state of relative metabolic quiescence

Fig. 1.24 Transmission electron micrograph of human adult sclera (×17,750), episcleral vessel. Note the continuous, thin vascular basement membrane and the lack of a vascular wall other than that formed by the endothelial cell, basement membrane, and the pericyte

Fig. 1.23 Transmission electron micrograph of human adult episcleral tissue (×7,500). Episcleral vessel (transverse section) with discontinuous pericyte support, and typical microvascular endothelium, are visible. A red blood cell is seen in the lumen

Fig. 1.25 Transmission electron micrograph of human adult sclera (×7,500). Episcleral vessel, with red blood cells in the lumen, endothelial cells lining the vessel, and supporting pericyte cytoplasm are visible. Note the scleral Þbroblasts and collagen underlying the vessel