Ординатура / Офтальмология / Английские материалы / Retinal and Vitreoretinal Diseases and Surgery_Boyd, Cortez, Sabates_2010

In vertebrate embryonic development, the retina and the optic nerve originate as outgrowths of the developing brain, so the retina is considered part of the central nervous system (CNS). It is the only part of the CNS that can be imaged directly.

The retina ranges in thickness from about 100-500 μm. It is a composite of numerous cellular and synaptic layers which can be grossly split into an outer epithelial layer (referred to as the retinal epithelium or retinal pigment epithelium) and an inner sensory layer (referred to as the sensory retina or neuroretina). The retina is one of the most metabolically active tissues in the body. Its major function is to convert light energy into chemical and electrical energy so that vision can occur (if a functional brain is present).

The retina is a complex, layered structure with several layers of neurons intercon-

nected by synapses. The only neurons that are directly sensitive to light are the photoreceptor cells. These are mainly of two types: the rods and cones. Rods function mainly in dim light, while cones support daytime vision. A third, much rarer type of photoreceptor, the photosensitive ganglion cell, is important for reflexive responses to bright daylight.

Neural signals from the rods and cones undergo complex processing by other neurons of the retina. The output takes the form of action potentials in retinal ganglion cells whose axons form the optic nerve. Several important features of visual perception can be traced to the retinal encoding and processing of light.

Functional Anatomy

The vital structures of the retina are conveniently arranged for us in distinct

layers. These are clearly shown in Figure 1. The order of retinal layers starting from outer to inner layers (that is, from choroid to vitreous) is as follows: Retinal pigment epithelium, Photoreceptor outer segments, Photoreceptor inner segments, Outer or external limiting membrane, Outer or external nuclear layer, Outer or external plexiform layer, Inner nuclear layer, Inner plexiform layer, Ganglion cell layer, Nerve fiber layer, Internal limiting membrane.

The outermost layers next to the choriocapillaris are Bruch́smembrane and the retinal pigment epithelium (RPE). Bruch’s membrane allows passage of nutrients from the choriocapillaris to the retina, while acting as a barrier to invasion of the retina by its vessels. The RPE are supporting cells for the neural portion of the retina and are important for photopigment regeneration. The RPE is dark with melanin, which decreases light scatter within the eye. The rod and cone layer contains the outer and inner segments of the rods and cones photoreceptors. The outer limiting membrane orders these from the outer nuclear layer (ONL) - the cell bodies of rods and cones. Next, we see the outer plexiform layer (OPL), with the rods and cones axons horizontal cell dendrites, and bipolar dendrites. The inner nuclear layer (INL) contains the nuclei of the horizontal and bipolar cells. The inner plexiform layer (IPL) neatly contains the axons of the bipolar cells (the amacrines), and the dendrites of the ganglion cells. The layer of ganglion cells (GCL), is covered by the layer of the optic nerve fibers - fibers from ganglion cells traversing the retina to leave the eyeball at

the optic disk. Finally, the internal limiting membrane forms the border between the retina and the vitreous.

There are two distinct vascular systems in the ocular fundus: retinal and choroidal. The retinal vasculature is identified in Figure 1C as (U) and (V). The choroidal vasculature is identified in Figure 1C as W. Between them lies the retinal pigment epithelium (RPE), Fig. 1-C-X, an opaque monolayer of cells anterior to the choroid that normally largely obscures its vasculature from ophthalmoscopic view. Pathologic alteration of the structure and pigmentation of the RPE affects the pattern of choroidal fluorescence perceptible during angiographic studies. Familiarity with the anatomy and interaction of these anatomic layers is the key to accurate interpretation of fluorescein angiograms, an examination which is vital to the diagnosis of retinal diseases.

The photoreceptor cells (rods and cones), Figure 1C-K and T, are supplied with nutrients from the choroid (Figure 1C-W) through the retinal pigment epithelium (Figure 1C-X).

Choroid

supplied by the long and short posterior and recurrent anterior ciliary arteries and is

drained by the four mid-peripheral vortex veins (Figure 1C-W). The choroidal capillary system, the choriocapillaris, is located innermost (Figure 1C-Y), its basement membrane forming the outer layer of Bruch’s membrane. It has a lobular pattern, with central arterioles feeding capillary beds drained by peripheral venules.

The walls of the choroidal capillaries are extremely thin, with multiple fenestrations permitting passive fluid transport from the capillary lumen to the surrounding extravascular space. During fluorescein angiography studies, the fluorescein molecule is sufficiently small to pass readily and rapidly out of the choriocapillaris, but it does not pass through the overlying retinal pigment epithelium (Figure 1C-X).

Retinal Pigment Epithelium

of pigmented cuboidal cells which are

K-T) and forms a structural barrier between the sensory retina and choroid that, under normal circumstances, fluorescein dye will not cross.

Because of the presence of pigmented cells, the RPE serves as an optical barrier. Pigment density is not uniform across the whole retina. It is more intense in the macular region, where pigment epithelial cells are tall, columnar, and densely packed, and least in regions anterior to the equator, where these cells are flatter and have a sparsity of pigment granules.

Retina

The most important characteristics of the retina are its functional architecture and its light transmission and absorption properties. The retina is a thin transparent tissue perfused by vessels from the central retinal artery and, in about 30% of eyes, by an additional cilioretinal artery. The cilioretinal artery, when present, fills at the same time as the choroid. Unlike the choroid, the retinal capillaries are not fenestrated, and there is virtually no extracellular space between the densely packed retinal cells. As a result, the retinal vasculature constitutes a “closed system” that stands out in stark optical contrast to the surrounding tissue, especially in fluorescein angiography.

The outer nuclear and plexiform retinal layers of the retina (Figure 1C-Q) have a high concentration of yellow xanthophyll pigment, particularly in the macula, which is

about two disc diameters in size surrounding (but not including) the fovea (Figure 2). The fovea centralis, which lies at 3.5 mm lateral to the optic disc, is specialized for fine visual perception. In the fovea, the cells are all cones. The axons of the receptor cells pass directly to the inner side of the outer plexiform layer, wheretheyconnectwithdendritesofhorizontal and bipolar cells, extending from the inner nuclear layer. Selective absorption of blue light by this pigment produces a relatively darker macular background in fluorescein angiography.

The Normal Retina

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The retina receives its blood supply from two sources: the choriocapillaris and the central retinal artery. The choriocapillaris is a layer of capillaries intimately attached to the outer surface of Bruch́smembrane. The choriocapillaris supplies the outer third of the retina, including the outer plexiform and outer nuclear layers, the photoreceptors, the pigment epithelium and all of the fovea. The remaining inner two thirds of the retina is supplied by branches of the central retinal artery.

Optic Nerve

The optic nerve consists mainly of fibers derived from the ganglionic cells of the retina (Figure 3). These axons terminate in arborizations around the cells in the lateral geniculate body, pulvinar, and superior colliculus which constitute the lower or primary visual centers. From the cells of the lateral geniculate body and the pulvinar fibers pass to the cortical visual center, situated in the cuneus and in

the neighborhood of the calcarine fissure. A few fibers of the optic nerve, of small caliber, pass from the primary centers to the retina and are supposed to govern chemical changes in the retina and also the movements of some of its elements (pigment cells and cones). There are also a few fine fibers, afferent fibers, extending from the retina to the brain, that are supposed to be concerned in pupillary reflexes.

The Vitreous

The vitreous is a clear, avascular gelatinous body that fills the space bounded by the lens, retina and the optic disk. Its volume is approximately 80% of the entire globe (Figure 4). The vitreous is the largest single tissue of the human eye with an average volume of 5 ml. Though many people view the vitreous as a relatively inert and optically empty substance, it causes many ocular problems and is secondarily affected by

several retinal and choroidal disorders. The most common pathological vitreous condition is the posterior vitreous detachment.

The basic structure of the vitreous is 1% collagen and hialuronic acid molecules supported and compartmentalized by a gossamer sacular system of connective tissue; the rest is water. The outer surface-the hyaloid membrane is normally in contact with the posterior lens capsule, the zonular fibers, the pars plana epithelium, the retina and the optic nerve head. The base of the vitreous is

defined as the part in contact with the pars plana epithelium and the retina immediately behind the ora serrata.

Normal Appearance of the

Retina

Because the sensory retina is optically clear, ocular fundus appearance depends on retinal vasculature, degree of melanosis of the retinal epithelium and choroid, and presence or absence of a tapetum. Retinal epithelial cells overlying a tapetum usually are amelanotic so that this region of the ocular fundus appears as the color of the tapetum. In nontapetal regions or eyes having no tapeta, heavily melanotic retinal epithelial cells and choroid impart a dark brown hue to the ocular fundus. Less melanosis leads to lighter shades of brown. As the ocular fundus becomes lighter in color, the deeper structures, such as choroidal vessels or sclera, become

more visible. In some individuals there may be very little retinal epithelial melanin and moderate choroidal melanin so that choroidal vessels, which are somewhat orange and red compared with the red of retinal vessels, are visible in a background of brown. In amelanotic or mildly melanotic eyes, the choroidal vessels will be clearly visible with a white background which is, of course, the sclera.

Bibliography

1)Boyd, B. F., “Laser Surgery of the Retina – The Normal Retina.” World Atlas Series of Ophthalmic Surgery, English Edition, Vol. IV, 1999:87-88.

2)Boyd, S., “The Normal Retina”. Retinal and V itreoretinal Surgery – Mastering the Latest Techniques, English Edition, 2002:(1)1-4.

Fluorescein angiography has been extensively used for many years. Fluorescein patterns of nearly all the major retinal diseases have been described in numerous books and atlases published by well known retinal specialists. The presentation of this chapter is to provide a practical understanding of the vasculature of the retina, how it functions, identify the main fluorescein angiography patterns, both normal and abnormal, and when is laser treatment indicated.

McLean and Maumenee were the first to use fluorescein dye in living human subjects (1955). In January 1960 Novotny and Alvis performed the first human fluorescein angiogram, and they were the ones who developed the basic photographic system required for sequential documentation of flow through the fundus.

Fluorescein angiography enables us to supplement the information derived from direct clinical visualization with evidence of altered fluid dynamics in the iris, retina, and choroid and to diagnose structural changes in the retina and retinal pigment epithelium.

Several anatomic and physiologic features of the eye must be considered in the

interpretation of fluorescein angiograms. Blood vessels appear larger with angiography than with ophthalmoscopy or color photography. On angiography, the entire caliber of the vessel lumen can be seen, whereas with the other two methods, only the central blood column is visible, and not the marginal layer of clear plasma. Surrounding each retinal artery and, to a lesser extent, each retinal vein, is a small avascular zone. On a high-quality angiogram, the avascular zone around retinal arteries can be seen easily. Only in a few instances, however, can the avascular zone be seen around the veins.

The foveal capillary-free zone may be crossed by a large retinal vessel, but this is rare, and should be regarded as a variant of the normal pattern.

The visibility of the choroid is dependent upon the density and distribution of pigment in the retinal pigment epithelial cells and, to a lesser extent, upon the density of the choroidal pigment. Since the cells of the retinal pigment epithelium are taller and more heavily pigmented in the region of the macula, there is less fluorescence transmitted from the underlying choriocapillaris in this area.

Fluorescein leaks from the choriocapillaris permeates the choroid, and is partially absorbed by the sclera. Areas in which the pigment epithelium is deficient may show fluorescence from the sclera. If a scar is present in any area, it may be stained by fluorescein, causing it to fluoresce.

In a normal eye, the optic nerve head is fluorescent after the passage of dye from the circulatory system. Dye from the choriocapillaris at the margin of the nerve head permeates the nerve head. Because there is some degree of normal fluorescein leakage from the ciliary body, the anterior chamber and vitreous also will contain some dye.

According to experts, five factors are interrelated to obtain the most value from fluorescein angiography:thephysicalandchemicalproperties of fluorescein dye, the anatomy of the human eye, the proficiency of the photographers, the sophistication of the recording equipment, and (most critically) the skill of the professional at correctly interpreting the information and relating it to other clinical findings.

The Fluorescein Dye

Clinical and Physical Properties

Sodium fluorescein is a stable, highly water-soluble, pharmacologically inert, inexpensive and relatively safe substance. It fluoresces at normal blood pH, and absorbs and emits light within the visible range of the spectrum, permitting the use of standard photographic equipment and supplies.

Physiologically the sodium fluorescein molecule is small enough to diffuse rapidly within fluid compartments yet sufficiently large not to pass through the tight endothelial junctions of intact retinal blood vessels and the retinal pigment epithelium. When stimulated

by light, this dye re-emits light of a longer wavelength and lower energy level almost instantaneously.

How to Use It

The solution is injected intravenously. There are several alternatives for its administration:

1)Use a solution of 10% sodium fluorescein (5 ml).

2)Use a 25% solution in smaller quantities. Some investigators have obtained equally satisfactory results, with fewer adverse effects with this second alternative, or even smaller injections (2 ml) of the standard 10% solution (Table 1).

Table 1. Normal Circulatory Filling

0sec — injection of fluorescein

5mins — late staining

Fluorescein enters the ocular circulation from the internal carotid artery via the ophthalmic artery. The ophthalmic artery supplies the choroid via the short posterior ciliary arteries and the retina via the central retinal artery, however, the route to the choroid is typically less circuitous than the route to the retina. This accounts for the short delay between the “choroidal flush” and retinal filling.