quickly than do rods. The state of adaptation (sensitivity) of a photoreceptor is regulated by Ca++, which can influence the concentration of cGMP, the messenger that controls gated ion channels in the photoreceptor membrane.78

Circadian Rhythm

The circadian rhythm is the light/dark or wake/sleep cycle, which usually extends over a period of 24 hours. It is under the direction of pineal melatonin secretion, which is influenced by the suprachiasmatic nucleus, the master biologic clock located in the hypothalamus.114 A special population of ganglion cells that contain melanopsin has been identified; they are photosensitive and can respond directly to light. It is estimated that there are 3000 of these ganglion cells dispersed across the retina.115,116 Their axons project to the suprachiasmatic nucleus and help in synchronizing the circadian rhythm to the wake/sleep cycle.78,116 Neuromodulators, such as dopamine, secreted by the interplexiform neuron and the amacrine A18 cells, may also have some role in regulating the circadian rhythm.113

Retinal Metabolism

The extensive network of continual intracellular communication requires extensive energy utilization by retinal tissue. The primary source of energy is provided by glucose metabolism. Glucose moves out of the blood and into retinal tissue via facilitated diffusion; glucose transporters are located on both the apical and basal membranes of the retinal pigmented epithelial cell and on the endothelium of retinal capillaries.27 The retina can switch from glycolysis to oxidative metabolism depending on need, but even under normal physiologic conditions the retina has a high rate of anaerobic glycolysis.78 The monophosphate pathway is particularly active in photoreceptors for rhodopsin regeneration and ribose production for nucleotide synthesis.27 Müller cells store glycogen, providing a ready source for glucose. Because energy requirements are high, oxygen consumption is high. Capillary blood flow in retinal tissue has been measured in primates and is approximately 60 ml/min/100 g of tissue, similar to the flow in the brain.117 Oxygen utilization by photoreceptors is 3 to 4 times higher than other CNS neurons.27 Because oxygen must diffuse from the choriocapillars to the inner segments where the mitochondria are located, blood flow is significantly higher in the choriocapillaris, i.e., approximately 2000 ml/min/100 g of tissue.116 In dark, the photoreceptors consume so much oxygen that the oxygen tension in the tissue is near zero and the photoreceptors are operating under near ischemic conditions.78

R E G I O N S O F R E T I N A

The retina is often described as consisting of two regions: peripheral and central. The peripheral retina is designed for detecting gross form and motion, whereas the central area is specialized for visual acuity. In area, the periphery makes up most of the retina, and rods dominate. The central retina is rich in cones, has more ganglion cells per area than elsewhere, and is a relatively small portion of the entire retina.

Clinical Comment: Peripheral

Vision

When the eyes are looking straight ahead, the object of interest is imaged on the macular area in the central

retina, and the rest of the field that is in view, sometimes described as that seen “out of the corner of one’s eye,” is focused on more peripheral retinal regions. Detail and color of those objects in the central area of vision are evident, but the objects in the periphery are less clear. The periphery is quite sensitive to change, and even slight movement in the more peripheral areas often stimulates the retina and frequently elicits a turning of the eye or head toward the motion.

CENTRAL RETINA

Macula Lutea

The macula lutea appears as a darkened region in the central retina and may seem to have a yellow hue because of the xanthophyll pigments, lutein, and zeaxanthin.52,118 These pigments are located throughout the retina, but the greatest concentration is in the macula. The pigments are primarily located in the photoreceptor inner fibers but are also found in the rod outer segments.78,118,119 The newborn has little if any of these pigments, but they gradually accumulate from dietary sources. These pigments apparently act as filters, absorbing short wavelength visible light to reduce chromatic aberration but may also have an antioxidant effect, suggesting a protective role against UVR damage.118 The macula lutea is approximately 5.5 mm in diameter; its center is approximately 3.5 mm lateral to the edge of the disc and approximately 1 mm inferior to the center of the disc. The pigment epithelial cells are taller and contain more pigment than cells elsewhere in the retina, contributing to the darkness of this area. However, the density of the pigment varies greatly from person to person.58 The choroidal capillary bed also is thicker in the macula lutea than elsewhere.

Useful color vision occupies an area approximately 9 mm in diameter, the center of which is the macula lutea.8 The entire macular region consists of the

foveola, the fovea, and the parafoveal and perifoveal areas (both are annular regions) (Figure 4-26). These areas are described and delineated on the basis of histologic findings, with consideration given to the number and rows of cells in the nuclear layers. However, these areas are not easily differentiated on viewing the living retina.

Clinical Comment: Terminology

The terms used to describe the macular area differ between the histologist and the clinician. The histologist uses the word fovea to describe what a clinician would name macula, and the histologist calls the foveola that which

a clinician would name the fovea. The term macula is purely a clinical one and usually refers to the area of darker coloration that is approximately the same size as the optic disc; clinically, the term fovea then refers to the very center of this area. The posterior pole is another term used in clinical descriptions of the fundus. There is no universal agreement regarding its definition, and its usage varies from clinician to clinician.29

Fovea (Fovea Centralis)

The shallow depression in the center of the macular region is the fovea, or central fovea of the retina (fovea centralis retinae). This depression is formed because the retinal neurons are displaced, leaving only photoreceptors in the center. The fovea has a horizontal diameter of approximately 1.5 mm. The curved wall of the depression is known as the clivus, which gradually slopes to the floor, the foveola. The fovea has the highest concentration of cones in the retina; estimates vary from 199,000 to 300,000 cones per square millimeter.96,120 The number falls off rapidly as one moves away from the fovea in all directions. In this area of the retina, specialized for discrimination of detail and color vision, the ratio between cone cells and ganglion cells approaches 1:1.8 In more peripheral areas of the retina, which are sensitive to light detection but have poor form discrimination, there is a high ratio of rods to ganglion cells.

Within the fovea is a capillary-free zone 0.4 to 0.5 mm in diameter (Figure 4-27).121 The lack of blood vessels in this region allows light to pass unobstructed into the photoreceptor outer segment.

The only photoreceptors located in the center of the fovea are cones. These are tightly packed, and the outer segments are elongated, appearing rodlike in shape yet containing the visual pigments of the cone population. The external limiting membrane is displaced vitreally because of the lengthening of the outer segments. This rod-free region has a diameter of approximately 0.57 mm1 and represents approximately 1 degree of visual field.120 Most of the other retinal elements are displaced, allowing

Foveola

Fovea

Parafoveal area

Perifoveal area

FIGURE 4-26

Schematic showing regions of retina and corresponding histologic architecture.

light to reach the photoreceptors directly without interference of other retinal cells (Figure 4-28).

The cells of the inner nuclear layer and ganglion cell layer are displaced laterally and accumulate on the walls of the fovea. The photoreceptor axons become longer as they deviate away from the center; these fibers are called Henle’s fibers. They must take an oblique course to reach the displaced bipolar and horizontal cells (Figure 4-29). This region of the OPL is known as Henle’s fiber layer.1 The retinal layers and the foveal indentation are clinically evident with a CRT view of the retina (Figure 4-30).

Foveola

The diameter of the foveola is approximately 0.35 mm. At the foveola, the retina is approximately 0.13 mm thick, compared with 0.18 mm at the equator and

FIGURE 4-27

Clinical Comment: Central Foveal

Reflex

Capillary bed of macular region, with capillary-free zone (a) in its center. (×42.5.) (From Hogan MJ, Alvarado JA, Weddell JE: Histology of the human eye, Philadelphia, 1971, Saunders.)

FIGURE 4-28

Light micrograph of the foveal region. The indentation caused by the absence of several retinal layers is evident.

Internal limiting membrane

Nerve fiber layer

Ganglion cell layer

IPL

INL

OPL

ONL

External limiting membrane

Photoreceptor layer

RPE

Choroid

When the direct ophthalmoscope light shines directly into the fovea, it reflects a pinpoint of light called the central foveal reflex. This pinpoint reflection is caused by the parabolic shape formed by the clivus. Because the shape of the fovea is not always exactly parabolic, the reflection may vary in sharpness and regularity from person to person. The fovea is the site at which the object of interest is imaged. In younger persons the sheen from the internal limiting membrane sometimes is seen as a circular macular reflex (see Figure 4-18).

Clinical Comment: Metamorphopsia

The axis of the photoreceptor outer segment is oriented to accomplish capture of incident light rays. If a disruption occurs so that the outer segment is no longer oriented toward the exit pupil, vision may be altered. With macular edema, the orientation of the photoreceptors is changed, and metamorphopsia can often be elicited with an Amsler grid.122