Anatomic Subdivisions
The retina is a delicate transparent tissue of maximal thickness (approximately 0.55 mm) at the foveal margin and minimal thickness (0.13 mm) at the umbo. Anatomically the macula (macula lutea or central retina) is defined as that portion of the posterior retina that contains xanthophyll and two or more layers of ganglion cells. It measures approximately 5.5 mm in diameter and is centered approximately 4 mm temporal to and 0.8 mm inferior to the center of the optic disc ( Figure 1.01 ). On the basis of microscopic anatomy, the macular area can be further subdivided into several zones. The fovea (fovea centralis) is a depression in the inner retinal surface in the center of the macula. It measures approximately 1.5 mm (1500 μm) or one disc diameter in size. The central floor of the fovea is called the foveola. It measures approximately 0.35 mm in diameter. It lies within the capillary-free zone or foveal avascular zone, which measures approximately 0.5 mm (500 μm) in diameter in most patients. A small depression in the center of the foveola is called the umbo. A 0.5-mm-wide ring zone where the ganglion cell, inner nuclear layer, and outer plexiform layer of Henle are the thickest is called the parafoveal area. This zone is in turn surrounded by a 1.5-mm zone referred to as the perifoveal area.
Clinical Appearance
Ophthalmoscopically, the anatomic subdivisions of the macula are ill defined ( Figure 1.02 ). The center of the macula appears as a poorly defined, one-fourth to one disc diameter size zone of greater pigmentation that is maximum in the foveolar area. The foveal reflex, which is present in most normal eyes, appears to lie just in front of the center of the foveola and therefore overlies the anatomic umbo. There are no consistent ophthalmoscopic landmarks to indicate the margins of either the 0.35-mm diameter foveola or the 1.5-mm diameter fovea. The margins of the capillary-free zone of the retina that in most patients measures approximately 500 μm in diameter angiographically can only be estimated biomicroscopically because the perifoveolar capillary network is not visible. In younger patients an oval or round halo light reflex at the inner retinal surface may correspond with the foveal margin ( Figure 1.02B ). The foveal depression can be visualized with the narrow slit-lamp beam.
Blood Supply
Retina
The blood supply to the inner half of the retina is by way of the central retinal artery, which usually divides into a superior and inferior trunk within the optic nerve head. These trunks divide into two branches, one supplying the nasal and the other the temporal quadrant of the retina. The corresponding retinal venous branches have much the same distribution as the arteries. These major blood vessels lie in the nerve fiber layer close to the internal limiting membrane of the retina. They give off arteriolar and venular branches that posteriorly occur primarily at right angles to the parent vessel. The branching is predominantly dichotomous as they course peripherally. The right-angle branches are referred to as first-order arterioles and venules ( Figure 1.02A ). In approximately 20% of patients Justice and Lehmann found that a variable portion of the papillomacular area was supplied by one or more cilioretinal arteries derived from the ciliary circulation ( Figure 1.02A ). Occasionally a large cilioretinal artery may supply virtually the entire macula. The retinal arterial circulation is ordinarily an end-artery system that does not communicate with the blood vessels of the choroid or ciliary body. The retinal arteries and veins are interconnected via an extensive capillary network that extends outward to the external border of the inner nuclear layer. The blood vessel walls are normally transparent. The postcapillary venules join to become retinal veins that accompany the retinal arteries and exit through the lamina cribrosa and drain into the superior ophthalmic vein. The retinal pigment epithelium (RPE) and the photoreceptors are nourished by diffusion from the choriocapillaris.
Choroid
The ophthalmic artery, the first branch of the internal carotid artery, divides into medial and lateral posterior ciliary arteries. Before entering the sclera each of these divides into one long posterior ciliary (LPCA) and 5–10 short posterior ciliary arteries (SPCA). A total of two LPCA and 15–20 SPCAs are thus formed. The LPCAs pierce the sclera 3–4 mm from the optic nerve and course between the choroid and the sclera along the 3 and 9 o’clock meridians till they branch at the ora serrata. Three to five branches bend posteriorly and supply the choroid till the equator. The SPCA enter the sclera around the optic nerve and course for a short distance in the suprachoroidal space, then enter the peripapillary choroid and branch anteriorly and posteriorly to supply the choroid up to the equator. There are seven anterior ciliary arteries (ACA) that accompany the four rectus muscles, about 8–12 recurrent branches of the ACA supply the anterior choriocapillaris, and the rest of the ACA form the major circle of the iris.
The venous drainage of the choroid is mostly through the vortex veins and a small anterior portion occurs through the anterior ciliary veins. Postchoriocapillaris venules form afferent veins that converge into the ampulla of the vortex veins (2 mm wide and 5 mm long) in each quadrant. Each quadrant has one vortex vein; occasionally more than one is present. They are situated 3–3.5 mm behind the equator ( Figure 1.06D ) and drain into the superior and inferior ophthalmic veins. The superior ophthalmic vein drains a major part of the globe and enters the cavernous sinus after passing through the superior orbital fissure while the inferior ophthalmic vein enters the pterygoid plexus via the inferior orbital fissure.
Choriocapillaris
The choriocapillaris have unique features compared to capillaries elsewhere in the human body. They are 40–60 μm in diameter, as opposed to other capillaries that are 5–10 μm in size, and have thin walls with fenestrations measuring 600–800Å. The fenestrations have a thin covering diaphragm and are more numerous on the internal side than the external side, which has the endothelial cell nuclei. Three to four red blood cells can pass through the choriocapillaris at a time. Pericytes are seen occasionally and gap junctions are present. Connective tissue, fibroblasts, and nerve fibers are present between the capillaries and provide support. There is a rapid transition from the arterioles to the capillaries, hence the large blood flow in the choroid. There is a central precapillary arteriole that breaks up into a lobule of choriocapillaris and empties into a peripheral postcapillary venule. There is regional variation in the choriocapillaris architecture. The lobular pattern of the choriocapillaris is seen in the posterior pole, whereas near the equator the precapillary arteriole and postcapillary venule have a more direct connection through the capillaries, and anteriorly the choriocapillaris connects the arterioles and venules at right angles, creating a ladder-like pattern.
The RPE is more highly pigmented in the central macular area than elsewhere. Whereas the amount of melanin in the RPE is similar in all races, the number of melanocytes and the amount of melanin in the choroid are greater in more highly pigmented races. In caucasians the combination of the pigment in the RPE and the choroid imparts an orange or orange-red color to the fundus. In most pigmented individuals the RPE and choroidal pigment impart a brown color that obscures most or all of the choroidal vascular details throughout the posterior fundus. Even in very blond individuals, in whom much of the choroidal vasculature is visible, the choroidal blood vessels in the macular region usually are obscured by the greater density of the RPE centrally ( Figure 1.02B ). RPE becomes less pigmented with age, and in brunette patients the greater contrast between the larger choroidal vessels and the surrounding melanocytes gives a tesselated appearance to the fundus ( Figure 1.02C ). Often there is less pigmentation of the choroid and RPE in a segmental area of the fundus inferior to the disc in the area of closure of the fetal fissure. Uneven distribution of melanocytes in the uvea may occasionally give a distinct heterochromic appearance to the fundus ( Figure 1.02D ).
Gross Anatomy
Examination of the macular area with a dissecting microscope is possible after making a coronal section through the pars plana of a fresh eye ( Figure 1.03 ). The retina begins to lose its normal transparency within hours of death. Yellow pigment is apparent in the center of the macula. It is highly concentrated in the foveolar area ( Figure 1.03A ). If the central macular area of a fresh human retina is viewed in cross-section, the concentration of the xanthophyll appears to be maximal in the outer nuclear and outer plexiform layers. Xanthophyll is also present, however, within the inner plexiform layer inside the foveal area ( Figure 1.04 ). In monkeys the yellow pigment has been localized by spectrophotometric analysis to all layers from the outer nuclear layer inward but with the greatest concentration in the outer and inner plexiform layer centrally. Microdensitometry of retinal sections of primate retinas suggests that the greatest concentration is in the cones axons centrally. Stereochemical analysis has demonstrated evidence that xanthophyll comprises two carotenoids with properties identical to those of zeaxanthin and lutein. After removal of the semitransparent retina, the normal orange-red appearance of the fundus is restored ( Figure 1.03B ). This color results primarily from the melanin within the RPE cells and not, as often implied, from the blood within the choroidal vessels. The relatively dark area in the foveal region is probably caused primarily by the increased pigment content of the RPE cells. The relative darkness of this area, along with the normal orange-red color of the surrounding fundus, largely disappears after the RPE is removed with a cotton applicator ( Figure 1.03C ). Some of the relative darkness of the central macular area remains, however, because of the greater concentration of choroidal melanocytes in this area. The large choroidal vessels in older patients appear as yellowish white cords coursing through the macular area. This loss of choroidal vessel wall transparency in older patients, although often referred to as “choroidal sclerosis,” probably represents a normal aging change in the choroidal vessel wall and is not associated with significant narrowing of its lumen.
After removal of the choroid, the entrance sites of the short and long posterior ciliary arteries are visualized ( Figure 1.03D ). The short posterior ciliary arteries are concentrated in the macular area, particularly along the temporal margin of the fovea and the peripapillary area. In the choroid they branch frequently and course outward toward the periphery. Several short posterior ciliary arteries enter nasal to the optic disc. The temporal long posterior ciliary artery and ciliary nerve enter about 1½ disc diameters temporal to the center of the fovea. Melanocytes are concentrated along either side of both of these structures.
Histology
The specialized structure in the macular region accounts for the predilection of certain disease processes to involve this area and for the variety of ophthalmoscopic changes peculiar to this area. In the macula we find the thickest portion of the retina ( Figure 1.01B ) surrounding the thinnest portion, the foveolar area. The normal retina is composed of a mass of interwoven neural cells with little extracellular space. The relative lack of extracellular space is apparent only with electron microscopy, which demonstrates cell membranes not visible with ordinary histologic techniques. In the inner half of the retina there is extensive intertwining of horizontally and vertically coursing neural cell processes and blood vessels, all of which are enveloped by lateral extensions of the Müller cell processes. In the outer plexiform layer of Henle, however, the long Müller and receptor cell processes radiate in an almost horizontal and then oblique direction away from the central foveal area and are not interconnected by intertwining neural processes and blood vessels. The Müller cells are modified glial cells that provide the structural framework supporting the neural elements of the retina. Their nuclei lie in the inner nuclear layer. Anteriorly their basal cell processes constitute the inner retinal surface, which is lined anteriorly by the so-called internal limiting membrane, basement membrane, or basal lamina of the Müller cells ( Figure 1.05 ). This membrane is relatively thick in the macular region except in the area of the foveola, where it is visible only by electron microscopy. The internal limiting membrane serves as an anchoring structure for the collagen framework of the vitreous. The apical or outer cell processes of the Müller cells extend external to the outer nuclear layer, where they are connected to the visual cells by a system of terminal bars that constitute the external limiting membrane ( Figure 1.05B ). This row of tight junctions probably provides at least a partial barrier to the passage of large molecules in either direction. It probably functions on the one hand to protect the retinal extracellular compartment from encroachment by subretinal exudate and on the other hand to prevent intraretinal exudate from spreading into the subretinal space.
