1 Anatomy of the Vitreous, Retina, and Choroid


1 Anatomy of the Vitreous, Retina, and Choroid

Hermann D. Schubert and Marilyn C. Kincaid, 1st edition chapter written by Marilyn C. Kincaid and W. Richard Green

1.1 Introduction

It is a truism that the anatomy of an organ, structure, or system provides the substrate for the types of pathologic processes that can affect it. This is particularly true for the retina and its associated structures, the vitreous and choroid. Understanding their structures allows the clinician to better understand diseases that can affect them and to appreciate the studies used to elucidate those diseased conditions.

1.2 Vitreous

The vitreous is a clear gel occupying the bulk of the eye, extending posteriorly from behind the lens and adhering to the internal limiting membrane of the retina (Fig. 1-1). This connective tissue comprises 80% of the total volume of the globe, about 4 mL. Normal vitreous allows visible light to pass to the retina without alteration or scatter. It also acts as a stabilizer, pressure regulator, shock absorber, and metabolic sink supporting the retina.

Fig. 1.1 Normal, youthful vitreous gel and associated landmarks.

On clinical examination, the collagenous vitreous is not homogeneous. Centrally, Cloquet’s canal, a space about 1 to 2 mm in diameter, extends from just behind the lens posteriorly to the optic nerve head. It is a remnant of the embryonic hyaloid vascular system. This canal has an S-shaped course from anterior to posterior, making a dip inferiorly before rising back to the nerve head. Anteriorly, it widens as Berger’s space to form the back surface of the patellar fossa.

The anterior cortical gel of the vitreous is the vitreous surface adjacent to the lens zonules and the posterior lens capsule. Biomicroscopically, the borders and structures of the gel may resemble a membrane, but ultrastructurally it consists of denser aggregations of collagen fibers. 1 The hyaloideocapsular ligament of Wieger is a circular attachment between the orbiculoposterior zonular fibers and the posterior surface of the lens capsule. It is not a true ligament, 1 and the attachments become weaker with age. The potential space formed between the lens and the patellar fossa bounded by Wieger’s ligament is called Berger’s space. A separation of Wieger’s ligament from the lens represents an anterior vitreous detachment.

Posteriorly, the canal widens to cover the area of Martegiani, which corresponds to the surface of the optic nerve head. The vitreous is firmly attached to the margin of the area, although with age the firmness of this attachment becomes attenuated. If the vitreous detaches completely, the glial peripapillary attachment is sometimes visible as a partial or complete ring suspended in the midportion of the eye, sometimes referred to as a Weiss ring.

The vitreous consists of about 99% water; the remaining compounds include hyaluronic acid and collagen, as well as inorganic salts and ascorbic acid.

Most of the vitreous collagen is concentrated peripherally in the vitreous body, adjacent to lens, retina, and optic nerve head. This denser portion of the vitreous is called the vitreous cortex. The remainder of the nuclear vitreous, located more centrally, has less collagen. The vitreous collagens are similar, although not chemically identical, to collagens elsewhere in the body. 2 The principal collagen component is type II; this is similar to the type II collagen of cartilage and suggests a support function. Type IX collagen is a minor component, also similar to the type IX collagen of cartilage.

Unlike collagen, the concentration of hyaluronic acid and other compounds is constant throughout the vitreous. The hyaluronic acid acts as a cross-link interposed between parallel fibrils of collagen forming a gel. Within the vitreous, especially in the cortex, are oval-to-spindle-shaped cells called hyalocytes. These cells contain organelles of synthesis and transport; in particular, they have abundant Golgi apparatus. The hyaluronic acid is believed to be synthesized in hyalocyte granules and secreted by these cells. 1

The vitreous base overlies the posterior aspect of the pars plana and adjacent anterior aspect of the ora serrata of the retina, and is thus a ring 4 to 6 mm in width. The vitreous collagen and its attachments are most dense at the vitreous base. Traction in this area may tear the peripheral retina and adjacent pars plana epithelium. 3 The ophthalmoscopically visible phenomena of white-without-pressure and white-with-pressure appear, in some cases, to be caused by the alignment of the collagen fibrils and their insertions. Adhesions between vitreous and retina have also been observed posterior to the base, particularly in older eyes. 3 Ultrastructurally, collagen fibers insert into the basal lamina of nonpigmented ciliary epithelium and into focal breaks in the retinal internal limiting membrane. 4

Controversial Points

  • The ophthalmoscopically visible phenomena of white-without-pressure and white-with-pressure in the retinal periphery may be caused by the alignment of the cortical vitreous collagen fibrils and their insertions onto the retina in the region of the vitreous base.

The vitreous is also attached to the internal limiting membrane of the retina around the center of the foveola and alongside the larger retinal vessels; however, these attachments are not visible clinically under normal conditions. Vitreous fissures are found in front of retinal vessels and a vitreous pocket is found in front of the papilla, connecting with the premacular bursa. 5 With age, as the formed vitreous detaches and collapses anteriorly, the resultant traction on the posterior vitreous base may cause tears in the retina, sometimes accompanied by a vitreous hemorrhage if a vessel is torn.

Recently, this classic concept of posterior attachment sites has been reexamined using in vivo swept-source optical coherence tomography, corroborating and extending findings based on postmortem injections. 6 Experimental studies suggest that the vitreous is more diffusely attached in the posterior pole, at least in younger people. 7 In a study of postmortem human eyes, the vitreous was mechanically lifted away from the retina. In older eyes, the vitreous detached smoothly from the retina, leaving the internal limiting membrane intact. Ultrastructurally, the vitreal side of the membrane remained smooth. In eyes younger than 20 years, the internal limiting membrane in the posterior pole region tended to detach along with the vitreous away from the underlying retinal layers, showing the vitreous–internal limiting membrane attachment to be stronger than intraretinal attachments.

1.3 Retina

The retina is the neuroepithelium of the eye responsible for receiving light and converting it into neural impulses, which are interpreted by the cerebral cortex. It is derived from the embryonic forebrain, and is part of the central nervous system. 8 The retina is a layered and highly ordered structure. The sensory retina is transparent, except for blood vessels, so the apparent color of the fundus is derived from the retinal pigment epithelial melanin, the melanin of the choroidal melanocytes, and the choroidal vessels.

Often, the terms retina and sensory retina are used interchangeably. The term retina properly includes the retinal pigment epithelium as well. Both the sensory retina and retinal pigment epithelium are derived from the bilayer of the optic cup. 9 Reflecting the embryonal invagination of the optic vesicle, the cells of Müllerian glia and retinal pigment epithelium are arranged apex to apex, with the respective basement membranes (inner limiting membrane and inner aspect of Bruch’s membrane) at opposite bases.

The outer neuroectodermal layer, the retinal pigment epithelium, remains a monolayer. It is discontinuous at the optic nerve head and continuous anteriorly with the pigment epithelium of the ciliary body.

The inner neuroectodermal layer proliferates, thickens, and differentiates to become the sensory retina. Except for the nerve fiber layer, the axons of which comprise the optic nerve, all layers of the sensory retina are discontinuous at the optic nerve head.

The sensory retina extends from the optic disc anteriorly to the ora serrata, where it is continuous with the nonpigmented ciliary epithelium. The ora serrata is located 6 mm behind the limbus, approximately at the insertion points of the rectus muscles, following the imaginary spiral of Tillaux. 10 The configuration of the ora serrata is discussed in more detail later.

1.3.1 Retinal Pigment Epithelium

The retinal pigment epithelium is one of the most biologically active tissues of the body. It is deeply pigmented, having become completely melanized by the sixth gestational week. Moreover, the degree of pigmentation is independent of race, unlike the pigmentation of the uveal tract, skin, and hair. 11 Biomicroscopically, this tissue is responsible for much of the color of the fundus. The macula appears darker, in part because the cells of this region are taller and narrower.

As seen in a flat preparation, the retinal pigment epithelium is a monolayer consisting of hexagonal cells with central round nuclei. Occasional cells have two nuclei, and such cells increase in number with age. Also, with age, the uniformity seen in young eyes gives way to cells more variable in size and shape. 12

Retinal pigment epithelial cells are polar—that is, each cell has a discernible base and apex (Fig. 1-2). Microvillous processes emerge from the apex of the retinal pigment epithelial cells to surround the photoreceptor outer segments. Some are fingerlike and slender, whereas others are broader and surround the outer segment like a bowl. 1 The cell nuclei are approximately spherical and lie just above the base of the cell. The unit membrane of the base is highly convoluted.

Fig. 1.2 Retinal pigment epithelial cells and the underlying Bruch’s membrane. BM, basement membrane; RBC, red blood cell; RPE, retinal pigment epithelium.

A variety of conditions, such as uveitis, trauma, and retinal detachment, can stimulate the retinal pigment epithelium to proliferate. The hyperplastic retinal pigment epithelium nonetheless retains its cytologic polarity, creating tubules, acini, and rows of cells, with accompanying basement membrane formation. 13 Peripherally, the retinal pigment epithelium may proliferate in various patterns in the aging eye. 14

Special Considerations

  • A variety of pathologic conditions, such as uveitis, trauma, and retinal detachment, can stimulate the retinal pigment epithelium to proliferate. Some degree of retinal pigment epithelial proliferation is also evident in the peripheral fundus of the otherwise normal aging eye, perhaps reflecting chronic tractional forces at the vitreous base.

Each retinal pigment epithelial cell is attached to adjacent cells by tight junctions. Ultrastructurally, these junctions include a zonula adherens and an adjacent zonula occludens, both situated near the apex of the cell and encircling it. 12 The zonula adherens is a gap junction. The unit membranes of two adjacent cells are close together, but each can be separately identified. The zonula occludens, as the name implies, has no intercellular space. The peripheral margins of the unit membrane appear fused. The result is that small molecules, such as fluorescein, travel inward from the choroidal circulation only as far as the apices of the pigment epithelial cells. This barrier is referred to as the outer blood–retinal barrier. 15 When the junctions are lost, leakage of fluid from the choroid may be clinically evident as an exudative retinal detachment. 16

In contrast to the convoluted unit membrane configuration at the base of the retinal pigment epithelial cell, the basement membrane is flat. It is the innermost component of Bruch’s membrane, a complex consisting of five layers discerned at the ultrastructural level (Fig. 1-2). 17 Extending outward from the retinal pigment epithelial side, these layers include the basement membrane of the retinal pigment epithelium, followed by a thick inner collagenous layer, an elastic layer, a thin outer collagenous layer, and the basement membrane of the choriocapillaris. Bruch’s membrane thickens with age 18 and also becomes somewhat more disrupted, so that individual layers become more difficult to discern.

Special Considerations

  • Ultrastructurally, Bruch’s membrane has five distinct layers. However, with age, a variable degree of membrane thickening and lipid deposition make these layers less distinct.

The retinal pigment epithelium is one of the most metabolically active tissues of the body. Reflecting this, numerous organelles of synthesis and transport are seen ultrastructurally in the pigment epithelium. Mitochondria are abundant, especially in the basal half of the cell, underneath its nucleus. Smooth and rough endoplasmic reticulum, free ribosomes, and Golgi apparatus are also evident. 1

A striking aspect of the pigment epithelium is its melanin pigment, mostly located in the apical cytoplasm of the cells. Two types of pigment granules are present in the retinal pigment epithelium- melanin and lipofuscin. Melanin is a dark brown to black pigment that is chemically poorly understood. The precursor is tyrosine, which is oxidized and polymerized through a series of enzymatic and nonenzymatic steps. Melanosomes, the site of melanogenesis, are round-to-oval membrane-bound granules morphologically similar to those of the uveal tract. In addition, there are elongated, lancet-shaped melanosomes. These granules are present in some of the apical microvilli; thus, they are in close proximity to the outer segments of the photoreceptors. 19 Recent evidence indicates that the epithelial cells do not produce additional pigment after birth, at least not through the tyrosinase enzymatic pathway. However, they do avidly take up free pigment in tissue culture. 20

Retinal pigment epithelial hypertrophy is usually congenital. The pattern can be either solitary or grouped; the latter is sometimes called “bear tracks.” The additional pigment is in the form of large, round melanosomes. 21 ,​ 22

The concentration of melanin varies regionally and also with age. The amount of melanin is actually greater at the equator than at the macula, where it is stacked up in taller and thinner cells, increasing optical density. With age, the melanin in peripheral pigment epithelium decreases, whereas that in the posterior pole remains constant for different age groups, resulting in overall greater optical density centrally. 23

Photoreceptor outer segments are shed daily and regenerated constantly throughout life, at a rate dependent on incident light. 24 ,​ 25 The shed material is engulfed and digested by the retinal pigment epithelium. However, this material is not completely digestible. 25 Lipofuscin- a complex of indigestible end products- is a golden yellow material distributed widely in the body. It is composed chiefly of vitamin A aldehyde adducts, although the composition varies even within the same tissue. With increased age, lipofuscin accumulates in the retinal pigment epithelium within secondary lysosomes due to ongoing phagocytosis. The melanosomes are displaced apically as the lipofuscin granules accumulate at the base. Complex granules containing both melanin and lipofuscin are called melanolipofuscin granules; in advanced age, these can be more numerous than the melanosomes. In the retinal periphery, this accumulation of lipofuscin and loss of melanin appears to be responsible for certain age-associated pigmentary patterns. Retinal pigment epithelial lipofuscin is also increased in recessive Stargardt’s disease and in age-related maculopathies. 24 ,​ 26


  • Accumulation of lipofuscin- with loss of melanin- in pigment epithelial cells of the retinal periphery appears to be responsible for certain age-associated pigmentary patterns.

There are no structural junctions between the retinal pigment epithelial cells and the photoreceptors. This is in contrast to the numerous tight junctions present between the corresponding two neuroepithelial layers of the ciliary body and the iris. 1 Instead, the epithelioretinal interspace contains a glycosaminoglycan matrix. Further, the retinal pigment epithelium constantly pumps fluid out of this space, creating a net negative pressure, to maintain photoreceptor apposition. This active transport accounts for about 70% of the total forces responsible for retinal apposition. 13 ,​ 24

In addition, interphotoreceptor matrix proteins act as a glue to keep the cells apposed. These protein adhesions are surprisingly strong in the freshly enucleated, and presumably in the living, eye. In experimental studies, the sensory retina was peeled from underlying pigment epithelium in freshly enucleated human and monkey eyes. If done within 1 minute of enucleation, the cone photoreceptor sheaths- components of the interphotoreceptor matrix- stretched to twice their normal size before their attachment to the pigment epithelium broke. 27

1.3.2 Sensory Retina

The sensory retina is distinctive for its highly ordered architecture, seen by light microscopy and optical coherence tomography (Fig. 1-3). Even at low microscopy power, three distinct bands of nuclei are readily evident, separated by tissue containing few or no cell nuclei.

Fig. 1.3 The sensory retina and retinal pigment epithelium (RPE). The photoreceptor outer segments (OS) and inner segments (IS) have their cell nuclei within the outer nuclear layer (ONL). They synapse with the neurons of the inner nuclear layer (INL) in the outer plexiform layer (OPL). These neurons, in turn, synapse with the ganglion cells (GC) in the inner plexiform layer (IPL). Axons from the ganglion cells form the nerve fiber layer (NFL). The internal limiting membrane (ILM) is the inner margin of the sensory retina. Hematoxylin and eosin, ×156.

Photoreceptor cells, both rods and cones, are unique, elongated cells; their nuclei comprise the outer nuclear layer of the retina. There are approximately 120 million rods and 6 million cones in the human retina. 28 Both rods and cones have specialized light-gathering ends- the outer segments- which represent specialized sensory cilia.

The rods are so named because the outer segment is cylindrical in shape. The stacked discs of the rods contain rhodopsin, the visual pigment for scotopic vision. The discs are separated from the surrounding unit membrane of the cell. The outer ends of the outer segments are constantly shed, taken up by the retinal pigment epithelium, and regenerated at the proximal end. 29

The cone outer segments are shorter than those of the rods, and thus they do not extend as closely to the pigment epithelial layer. The outer segment is tapered, giving the cone its name. However, in the fovea, the cones are not tapered, but instead are long, slender, and cylindrical in shape, allowing for tight packing. The stacked discs in cone photoreceptors generally remain continuous with the cell membrane. Cone discs are also shed and regenerated.

There are three types of cones, each type with its own spectral sensitivity; the light-sensitive proteins for these likewise reside in the stacked membranes of the outer segments. The proteins are chemically similar to opsin, the rod visual protein.

Connecting each outer segment to the inner segments is a nonmotile cilium. The inner segments, which connect the outer segments with their discs to the cell bodies, are filled with numerous mitochondria and other organelles of synthesis and transport. 29 The outer portion of the inner segment, containing the mitochondria, is called the ellipsoid. The inner portion of the inner segment is called the myoid. It contains smooth and rough endoplasmic reticulum and many microtubules. The inner segments of the cones are similar to those of the rods, but the ellipsoids are much larger and the mitochondria are several times more numerous. The presence of these organelles demonstrates the high metabolic activity and oxygen requirements of these cells. 1

The photoreceptor cells and adjacent Müller’s cells form tight junctions with each other. Because of the ordered cellular arrangement of the retina, these junctions are in line, forming what appears to be- at low power or on optical coherence tomography- a linear membrane, the external limiting membrane. However, it is not a true membrane, and ultrastructural examination reveals it to be a series of zonulae adherentes in a linear array. This close association between photoreceptors and Müller’s cells may be important for inner-segment metabolism. 1

Special Considerations

  • The external limiting membrane of the retina is not a true membrane. It represents a linear array of tight junctions (zonulae adherentes) located between the photoreceptor cells and adjacent Müller’s cells.

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May 23, 2020 | Posted by in OPHTHALMOLOGY | Comments Off on 1 Anatomy of the Vitreous, Retina, and Choroid
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