showed that the SPCAs are not terminal because the choriocapillaris is a single, continuous capillary vascular layer. Castro-Correia [6] was the first to describe rose-shaped arteriolar terminations. He thought that these vessels, although anatomically separated, were functionally interconnected. On the other hand, Hayreh [16] has advocated the presence of noncommunicating lobules. On the basis of fluorescein angiography findings, he described a mosaic of lobules, each one containing an arteriole in the middle and a venule at its periphery.

There is disagreement over the location of arterioles and venules in the lobules. Shimizu and Ujiie [36] confirmed the central location of the artery and the peripheral location of the venule. They specified the dimension of the lobules of the choriocapillaris: 200 mm in diameter at the equator, 100 mm at the posterior pole, and as small as 30–50 mm in the submacular region. On the contrary, Krey [22] and McLeod and Lutty [26], who performed histologic studies of the choriocapillaris stained with alkaline phosphatase reaction product, described a lobular organization of the choroid with arterioles and venules located peripherally and centrally, respectively. Uyama et al. [42] described the same lobular structure with a venule in the middle and arterioles in the periphery. Torczinsky and Tso [40, 41], in their histologic and fluorescein angiography studies of the choriocapillaris in albino monkeys, found structural differences between the posterior and peripheral choriocapillaris. Tilton et al. found that rat choriocapillaris had 50% less pericytes than retinal capillaries [39]. Also unlike retinal capillaries, pericyte loss did not occur in rat experimental diabetes [38]. Choriocapillaris is also unique in that the capillaries are fenestrated predominantly on the inner side, i.e., toward retina (Fig. 1.11). This probably is associated with the primary functions of this capillary system: transport of nutrients to RPE and photoreceptors and remove waste from disk shedding and RPE digestion of these disks.

The same sidedness has been observed in the location of VEGF receptors. Blaauwgeers et al. have reported that both VEGF receptor 3 (FLT-4)

Fig. 1.11 Ultrastructure of a human choriocapillaris lumen. The choriocapillaris is immediately posterior to Bruch’s membrane (top). Posterior to Bruch’s membrane is the basement membrane of the choriocapillaris endothelium, which is richly fenestrated on this side of the lumen. An elongated endothelial cell nucleus is present on the scleral side of the lumen (bottom), which contains RBCs. (Original magnification 11,800×) (From Rhonda Grebe, Wilmer Ophthalmic Institute, Johns Hopkins Hospital)

and VEGF receptor 2 (FLK-1 or KDR) are found on choriocapillaris endothelial cells on the retinal side [5]; however, we have not observed sided expression of VEGFR-2 in fetal or adult human choriocapillaris (unpublished results). Perhaps, sided expression of VEGF receptors is related to the basal production of VEGF by RPE. RPE was actually one of the first cells shown to produce VEGF and upregulate production during hypoxia [1]. Perhaps, the release of VEGF on the retinal side encourages maintenance of fenestrae on the choriocapillaris.

1.3Optic Nerve Vasculature

The central retinal artery is a direct branch of the ophthalmic artery. The central retinal artery is a small muscular artery with a luminal diameter of 170–245 mm. The ratio of the wall thickness to lumen is 1:4 in the pre–lamina cribrosa area to 1:10 post–lamina cribrosa [3]. There is a

subendothelial elastic lamina in the central retinal artery, but this is lost after it branches into the major arteries of retina. The central retinal vein has a luminal diameter of 200–245 mm and is classified as a medium caliper vein. It has a few pericytes, and the media has abundant elastic fibers. The papillary capillaries in the human optic nerve head range in size from 7 to 10 mm in lumenal diameter. They form a meshwork of vessels enclosing polygonal spaces in the nerve (Fig. 1.12). They have a typical capillary structure of endothelium, pericytes, and a basement membrane and are invested with astrocytes. However, there are less astrocytes associated with capillaries in the nerve head than at the level of lamina cribrosa.

Much of our knowledge of the optic nerve vasculature comes from the elegant and extensive work of Sohan Hayreh, which is nicely summarized in his Von Sallman Lecture and the source of the following information [18]. There is a great deal of variability in the arrangement of blood vessels in the optic nerve. Blood vessels at the surface of the optic disk are supplied by retinal arterioles. The prelaminar area, the area between the surface and lamina cribrosa, is supplied by the peripapillary choroid (Fig. 1.13). The blood supply is sectoral in this region and is

not from the peripapillary choriocapillaris or the central retinal artery. There is a dense capillary plexus (luminal diameters of 10–20 mm) in the lamina cribrosa region, which is supplied by the centripetal branches of the short posterior ciliary arteries or by the circle of Zinn and Haller (Fig. 1.13). From the corrosion casts of Fryczkowski [13] and Olver [31], the circle or perioptic nerve arteriolar anastomoses as Olver called it are supplied by the paraoptic short PCAs. Which PCAs supply it varies by individual, but in the majority of people it is the medial or lateral paraoptic short PCAs. The retrolaminar portion of the nerve is supplied by the pial vessels branches and sometimes branches from the central retinal artery. Therefore, the main source of blood for the optic nerve is from the PCA circulation via the peripapillary choroid and the short PCAs from the circle of Zinn and Haller. This yielded a blood supply of the optic nerve that has a sectoral distribution. The extremely variable pattern of distribution of the PCAs in the choroid and optic nerve may play a role in occurrence of optic neuropathies. Hayreh concludes that derangement of the posterior ciliary circulation in the optic nerve is responsible for most common ischemic optic neuropathies of the optic nerve head [18].