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R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM I. A NATOMY OF THE R ETINA Introduction The retina is the light-sensitive layer of the eye that, via the phototransduction that takes place in its rods and cones, first detects the image focused upon it by the eye’s optics, and then signals the brain about aspects of the real-world objects represented in that image. Together with the optic nerve, the retina comprises the “nervous tunic”-- the innermost of the eye’s three major tunics (connective = outer, vascular = middle). The English word “retina” comes from the Latin “rete,” which refers to a net or network. The retina is commonly considered to be central nervous system tissue displaced into the eye. 1. Functional Aspects of the Retina Nutritive: The retina has an extremely high metabolic rate, especially its photoreceptors. As a result, it enjoys an unusually abundant, dual supply of blood to 1) provide it with oxygen, 2) carry away its metabolites and 3) keep it from over-heating. Structural: The retina is a dense, compact, but very fragile tissue that is tenuously attached internally to the vitreous body and externally to the retinal pigment epithelium (RPE). The IOP normally acts to hold the retinal sheet smooth and in apposition to the RPE. The retina is thickest (560 µm) around the optic disc (i.e., in the peripapillary region), and thinnest peripherally (100 µm), where it merges with the ciliary body (pars plana) in the ora serrata region. Much of the structural integrity of the retinal tissue is owed to the presence of the Müller cells, a network of large glia whose cell bodies span its full thickness and branch extensively within its various layers. Neurophysiological: The retina not only transduces fluctuations in incident light energy to changes in neural membrane potential, it processes these neural signals and, via the long axons of its ganglion cells, conveys action potentials to neurons in numerous visual areas in the brain. Page 1 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM 2. Layers of the Retina Overview: Classically, the retina has been described as consisting of 10 “layers,” some of which contain the cell bodies of epithelia, neurons or glia, and others the processes (e.g., dendrites, axons) of neurons and their interconnections (i.e., synapses), and glia. Two were historically described as “membranes,” but are now understood to consist of the junctions between neurons and glia or glial expansions: (most external ) 1. Retinal Pigment Epithelium (RPE) 2. Rods and Cones (Photoreceptor Layer) 3. Outer (External) Limiting Membrane (OLM/ELM) 4. Outer (External) Nuclear Layer (ONL/ENL) 5. Outer (External) Plexiform Layer (OPL/EPL) 6. The Inner (Internal) Nuclear Layer (INL) 7. Inner (Internal) Plexiform Layer (IPL) 8. Ganglion Cell Layer (GCL) 9. Nerve Fiber Layer (NFL) 10. Inner (Internal) Limiting Membrane (ILM) (most internal ) Page 2 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Cell types in the mammalian retina Page 3 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM 1. Retinal Pigment Epithelium (RPE): The outermost (or most external) retinal layer consists of a single sheet of heavily pigmented, hexagonally-shaped epithelia – 46 million of them per eye. The RPE cells are smaller (~14 µm across), but more heavily pigmented, near the center of the retina than they are in the peripheral retina, near the ora serrata (~60 µm across). RPE cells undergo little postnatal mitosis; instead they stretch to accommodate growth of the globe and do not regenerate if they are lost. The RPE is critical to the normal functioning of the rod and cone photoreceptors, whose outer segments its cells partially engulf. The RPE’s functions include 1) maintaining the adhesion of the remainder of the retina, 2) providing a selectively permeable barrier between the choroid and the retina, 3) phagocytosis of the rod and cone outer segments, 4) synthesis of the inter-photoreceptor matrix, 5) absorption of stray light/reduction of scatter within the eye, and 5) transport and storage of metabolites and vitamins. Externally, Bruch’s membrane separates the RPE from the choriocapillary layer of the choroid. Page 4 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Page 5 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM 2. Rods and Cones (Photoreceptor Layer): The rod and cone cells are modified cilia containing specialized photo-labile pigments that are the key ingredient in the phototransduction process. Each eye contains 90-100 million rods and 4-5 million cones nonlinearly arrayed across the retina (see below). Each photoreceptor cell consists of 1) an outer segment that is partially engulfed by the RPE and contains a stack of discs impregnated with photopigment molecules, 2) an inner segment that is filled with mitochondria and is continuous with the cell’s nucleus and its axon, and 3) a narrow connecting cilium that joins the two segments. Page 6 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM 3. Outer (External) Limiting Membrane (OLM/ELM): The OLM lies in a 1µmthick plane at the internal end of the photoreceptor cells’ inner segments, separating them from their nuclei and synapses. Historically thought to be a fenestrated membrane through which the photoreceptors poked, the OLM is now known to consist of a two-dimensional array of adhering junctions (maculae adherens) between 1) photoreceptor inner segments and processes of Müller cells (glia), 2) adjacent processes of Müller cells, and 3) occasionally between neighboring inner segments. The OLM’s function is not certain, although it is clearly structural. It’s barrier-like feature also affects the way ionic currents flow around the photoreceptors. Page 7 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM 4. Outer (External) Nuclear Layer (ONL/ENL): The ONL contains the soma of the rod and cone photoreceptor cells with their nuclei. 5. Outer (External) Plexiform Layer (OPL/EPL): The OPL consists of the synaptic endings of the rod and cone photoreceptor cells onto the processes of the horizontal and bipolar cells, along with processes of the Müller cells (glia). 6. The Inner (Internal) Nuclear Layer (INL): Contains the soma (and nuclei) of the horizontal, bipolar and amacrine neural cells, as well as those of the Müller cells. 7. Inner (Internal) Plexiform Layer (IPL): The IPL consists of the processes and synapses of the bipolar, amacrine and ganglion cells, as well as processes of the Müller cells. Page 8 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM 8. Ganglion Cell Layer (GCL): This layer contains the nucleated cell bodies of the around 1.1 million ganglion cells that are found in each retina. 9. Nerve Fiber Layer (NFL): This layer is composed of the axons of the ganglion cells, which converge in a distinctive pattern from all parts of the retina to the optic disc (see below), where they leave the eye and form the optic nerve (CN II). These unmyelinated axons are surrounded by processes from astrocytic and Müller glial cells. 10. Inner (Internal) Limiting Membrane (ILM): The 1-to-2µm-thick ILM covers the internal surface of the entire retina (but not the optic disc), and is formed by the expanded “foot-like” processes of the Müller glial cells. Again, like the OLM, the ILM is not a true membrane but rather a barrier between the retina and the vitreous chamber. The collagen fibers of the vitreous body are adherent to the ILM, which can lead to traction on the internal surface of the retina and even retinal detachments as the collagenous portion of the vitreous shrinks with age. Page 9 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM 3. Regional Anatomy of the Retina Overview: The cells in the ten layers of the retina are not uniformly arrayed across the retinal sheet. Instead, the retina is characterized by distinct regional specializations, where not all the layers are present and the density of the different cell types varies dramatically. These areas of retinal specialization have a profound impact on the way our visual system perceives the outside world. Central Retina: Various terms are used to describe the 5-6mm-diameter region at the center of the retina that represents the central 180 of our visual field. Anatomists use specific changes in the histological features of the 10 layers of the retina to define the boundary of this central region and to distinguish several sub-regions within it. Clinicians use appearance of the funduscopic image, the architecture of the retinal blood vessels and linear dimensions (expressed in optic-disc-diameter units) to refer to some of these same regions. Macula/Macular Region/Central Retina/Posterior Pole: These terms are used (often rather loosely) to refer to the 5-6mm wide region of the retina at the posterior pole of the eye. Histologically, its peripheral limit is precisely defined as the point where the multi-layered ganglion cell layer is reduced to just a single layer of cells. The peripheral limit of this region is much harder to define based on gross anatomical changes or characteristics of the ophthalmoscopic image. Hence, clinicians typically refer to it as the approximately 4-disc-diammeter region whose center lies slightly below and 2.5-disc diameters temporal to the optic disc. Note that the nasal boundary of the macula is roughly tangent to the temporal rim of the optic disc. MACULA. This figure shows the relationship between the central retinal regions with the macula to their histological features. The boundaries of the regions as they appear in a fundus photograph are aligned with their equivalent histological landmarks in a meridional section of the retina. The fundus photograph indicates the locations of the foveola (a), fovea (b), parafovea (c) and perifovea (d). The approximate dimensions of these various regions are indicated in the space between the two images. Page 10 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Sketch, redrawn from the previous figure to show the location of the macula lutea and to indicate the number of rows of ganglion cells present within each region of the macula. Page 11 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Fovea (Central Fovea, Fovea Centralis): At the center of the macula lies the fovea, an approximately 1.5mm-diameter region whose center is located about 4mm temporal and 0.8mm below the center of the optic disc. The retina thins to a thickness of only about 130µm in the central fovea as its inner layers are progressively displaced centrifugally, toward the outer edge of the fovea. Thus, the central fovea contains only the RPE, photoreceptor, OLM, ONL, OPL and ILM layers. The fact that the bipolar cells to which the central foveal photoreceptors have to connect have been displaced to the sides means that the elongated axonal processes of the photoreceptors have to run obliquely to make their synapses. These radially oriented, elongated processes are stacked upon on each other, creating a new retinal layer in the fovea known as Henle’s fiber layer. There are only cone photoreceptors in the central 300µm (1o of visual angle) of the fovea, a subregion known as the foveola. These central foveal cones are highly elongated and narrow, so that they appear almost rodlike. They are also very densely packed -- their density reaches 200,000 cones/mm2. Thus, the foveola, which represents the central 1o of our visual field (your little finger, held at arm’s length, subtends about 1o), contains a total of only around 4,500 cones. The internal surface of the fovea is concave, and when viewed ophthalmoscopically its smooth ILM reflects and condenses light, creating the “foveal reflex.” This figure shows the displacement of the retinal layers, with the subsequent formation of Henle’s fiber layer, that occurs in the fovea. Page 12 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Parafovea: The 0.5mm-diameter annulus of retina immediately surrounding the fovea is known at the parafoveal. Henle’s fiber layer is very thick here and this region contains the highest density of neurons in the retina, owing to the displacement of cells out of the central fovea. Perifovea: The outermost annular ring of the macula, measuring 1.5mm in width, is known as the perifovea. Macula lutea: Within the macula, there is a zone centered on the fovea that measures about 2mm horizontally and 0.9mm vertically and is characterized by the presence of a special pigment (xanthophyll), which turns a bright lemon-yellow color in freshly excised retinas. This pigment, which is distributed throughout the retinal layers, is especially dense in the OPL, and is thought to provide protection to the retinal cells by filtering out potential harmful UV light. The macula lutea also gives rises to the clinically useful entoptic phenomena known as “Maxwell’s spot” and “Haidenger’s brushes.” Page 13 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Peripheral Retina: At its periphery, the retinal layers thin and ultimately merge with the layers of the ciliary body. Ora serrata: This term, which translates from the Latin to “serrated ring,” refers to the serrated (“teeth and bays”) appearance of the retinal termination at its border with pars plana of the ciliary body. The retina thins peripherally as its layers gradually disappear, proceeding generally from internal to external. The collagen fibers of the vitreous body are particularly well attached to the ILM near the ora serrata and this, together with its thinness and the normal degenerative changes it undergoes with aging (e.g., cystoid retinal degeneration), makes the retina susceptible to detachments in this region. Page 14 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Photograph of ora serrata region in an elderly patient. a) small or accessory ciliary processes of pars plicata of the ciliary body. b) typical dentate processes (or “teeth”) of the ora serrata, with “scalloped bays” in between. c) enlarged dentate process that forms a meridional fold (d) in pars plana of the ciliary body that merges with one of the major ciliary process of pars plicata (unlabeled white structures at top). e) cystoid retinal degeneration typical for eyes of this age. arrow) hole in the peripheral retina. Page 15 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Variations in the Density of Retinal Cells: The horizontal distribution of cells across the retinal expanse is highly non-uniform. Cone photoreceptors are at their highest density (about 200,000/mm2) in the foveola, where there are no rods. The rods reach their peak density (about 150,000/mm2) about 20o from the foveal center, near the outer edge of the macula. There are few-to-no ganglion cells in the foveola, and their density rises to its peak (about 35,000/mm2) around 1.5mm from its center, in the parafoveal region. Rod and cone density as a function of eccentricity along the retinal horizontal meridian. Photographs are optical sections through inner segments, showing rods and cones at different distances from foveal center. Distances (above each photograph) are in mm, and locations of various images are mapped onto rod and cone density curves below. Except for central image (0.0), which contains only cones, larger cells in each image are cones and smaller rods. Gap in nasal side of density curves marks location of optic nerve head. Page 16 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM 4. Blood Supply of the Retina Overview: The retina is extremely metabolically active, with the highest oxygen consumption (per weight) of any human tissue. Like the rest of the brain, the retina has a highly selective blood-tissue barrier that maintains a regulated homeostatic environment in this sheet of specialized neural tissue. The retina has a dual blood supply, with its inner layers (ILM, NFL, GCL, IPL, INL and OPL) being fed by branches of the central retinal artery, and its outer layers (ONL, , OLM, Photoreceptor and RPE) receiving blood from the choroid. Hence, reviewing the blood supply of the retina requires an understanding of the ocular blood supply. Central Retinal Artery and Vein: Typically the first branch of ophthalmic artery (itself the seventh branch of the internal carotid artery), the central retinal artery arises from the ophthalmic in the posterior orbit and runs beneath the optic nerve to a point 1213mm behind the globe, where it pierces the nerve, passes to the its center and emerges inside the eye at the center of the optic disc. In the eye, the central retinal artery bifurcates into superior and inferior branches, which run on the internal surface of the retina, in turn bifurcating into nasal and temporal branches. This bifurcating Page 17 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM branching pattern continues as the artery distributes blood across the retina in eversmaller branches. The central retinal vein and its branches accompany those of the artery. The central retinal vessels support four intra-retinal capillary beds (i.e., layers) that lie on both sides of the GCL and on both sides of the INL. An exception to this pattern occurs in the fovea, the central 500µm of which is capillary-free. The pathway taken into and out of the eye by the central retinal artery and vein, respectively. Funduscopic image showing optic nerve head, retinal arteries (lighter) and veins (darker) with their characteristic bifurcating branching pattern, and macular pigment. Note how vessels radiate across the retina nasal to the optic disc, but arch around the foveal region temporally. Page 18 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Page 19 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Choroid: Together with the iris and the ciliary body, the choroid forms the middle or vascular tunic of the eye, which is also known as the uveal tract. The choroid is to the retina as the pia and arachnoid maters are to the rest of the brain. The choroid’s principal function is to nourish the outer layers of the retina (ONL, , OLM, Photoreceptor and RPE), but it also helps to thermoregulate the photoreceptors and it absorbs stray light via its heavily pigmented outer region, which is known as the suprachorid. Internally, the choroid contributes to the formation of Bruch’s membrane, which lies between the choroid and the RPE. Blood is supplied to the choroid via branches of or derived from the ophthalmic artery, including the two long posterior ciliary arteries, numerous short posterior ciliary arteries and the seven anterior ciliary arteries. Blood is drained from the choroid via the four vortex veins, seven anterior ciliary veins and numerous pial veins. Progressing from external-to-internal through the choroid, the caliber of the blood vessels goes from large (in the external or Sattler’s region of the choroid) to medium (in the middle or Haller’s region) to capillaries (in the internal choriocapillary layer or choriocapillaris). The rate of transition from large vessel to capillary occurs more rapidly here than anywhere else in the body. The flattened capillaries of the choroid are extra-wide (capable of passing 2-3 RBC’s abreast) and fenestrated on their internal surfaces, and they are thought to be even more permeable than those elsewhere in the brain. Blood flows through them at a rate around seven times higher than that in the retinal capillaries. A) Diagram of choroidal blood supply. (LPCA – long posterior ciliary artery; SPCA – short posterior ciliary artery) B) Choroidal histology. (CC – choriocapillaris; HL – Haller’s Layer; SL – Sattler’s Layer) C) Plastic cast of choroid, viewed from external side. (VV – vortex vein) D) Diagram of “hexagonal units” in choriocapillaris fed by small arterioles. E) Plastic cast of choriocapillaris, viewed from internal side. Page 20 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Page 21 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Page 22 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Page 23 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Diagram illustrating the dual but essentially non-overlapping nature of the retinal blood supply. At the top, the choroid (via the choriocapillaris) nourishes the external retinal layers, including the RPE, OLM and photoreceptors (inner and outer segments). At the bottom, the central retinal artery and vein nourish the inner retinal layers, including the OPL, INL, IPL, GCL, NFL and ILM. Page 24 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM 5. Clinical Considerations of the Retina Retinal Imaging Techniques Funduscopy: The use of visible light to view the fundus of the eye (“funduscopy”) traces its origin to Helmholtz, who in 1851 realized that by peering at the eye through a peephole in a mirror held at 45o to the visual axis and shining light into the eye, he could see the light reflected from the retina. Ophthalmoscopy, as it came to be called, moved forward with the invention of the hand-held, direct illumination ophthalmoscope by Welch and Allyn in 1915. The principle of shining visible light onto the retina and viewing the reflected image is behind many modern viewing systems, including the binocular indirect ophthalmoscope (BIO) and fundus camera (see fundus image on page 18). Many aspects of the diagnosis and treatment of ocular (and even systemic) diseases still rely upon this 150-year-old technique for viewing the anatomical features of the fundus. Fluorescein Angiography: Although many of the larger blood vessels responsible for nourishing the retina can be viewed ophthalmoscopically, others are hidden by the retinal layers and/or too small to resolve. In addition, funduscopy provides limited information about the movement of blood through the intraocular vascular system. Fluorescein angiography utilizes the intravenous injection of a harmless fluorescent dye (sodium fluorescein) and video funduscopy performed with ultraviolet light to reveal the progression of fluorescein-labeled blood through the retinal vessels (arteries capillaries veins). Since the large dye molecule normally does not leak out of the retinal or choroidal capillaries, any dye left behind in the eye reveals places where seepage has occurred, and dye-free regions indicate areas where the circulation has been compromised. Diagram of the procedure for performing fluorescein angiography. Page 25 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Normal fluorescein angiographic images (from three different eyes). On the left, the arteries have filled and the veins are just beginning to fill. Note the slight lamination of the die in the veins. In the middle image, venous filling has progressed and lamination is more pronounced. The image on the right is from a slightly later stage in the procedure. The venous lamination is much less pronounced and the overall density of the die in the arteries and veins is similar. Optical Coherence Tomography (OCT): Tomography (from the Greek word tomos, which means "a section," "a slice" or "a cutting") refers to imaging of tissue produced by combining sections or slices. In OCT, changes in the coherence of light reflected from the fundus compared to that in a reference beam reflected from a mirror are used to generate noninvasive, in-vivo, 3-D images of the fundus tissues to a depth of 2-3mm. Current OCT methods can resolve structural details in the sub-micron range, delivering high-resolution images and quantitative analysis of tissues, including the retina. These images and the data provided by their analysis have greatly improved both the diagnosis and the treatment of retinal disease. OCT Instrument (Zeiss) Page 26 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM High-resolution images of the internal retinal structure can be taken with optical coherence tomography (OCT), and this figure demonstrates the processes involved in using this technology. (A) Low-coherence infrared light is transmitted into the eye through use of an interferometer. (B) The infrared light is transmitted through the pupil and then penetrates through the transparent layers of the retina. Subsequently, the light backscatters and returns through the pupil, where detectors can analyze the interference of light returning from the layers of the retina compared with light traveling a reference path of identical length (mirror #2). An algorithm mathematically uses this information to construct a gray-scale or false-color image representing the anatomy of the retina (shown in the upper right portion of the figure). (C) A fundus image from the OCT device, showing the optic disc appropriately centered and surrounded by the target image circumference marker for analysis of the retinal nerve fiber layer. Page 27 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM OCT image of normal retina. Cross-sectional image taken through the fovea. Top – Funduscopic image of normal retina. Bottom – Spectral OCT image from scan taken through the macula, showing foveal region, retinal layers and choroidal vessels. Page 28 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Top -- OCT image through foveal region of normal retina with computerized determination of the boundaries between major retinal layers. Bottom – Portion of top image, enlarged to show change in retinal layering in the foveal rim. Page 29 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Spectral OCT. 3D optical-coherence tomography (OCT) at 800 and 1060nm of (a)–(d) a normal retina and (e)–(h) a patient with retinitis pigmentosa. (b, f) High-definition (4096 depth scans) 800nm 3D OCT scan over 35°. (d, h) High-definition (2048-pixel) 1060nm 3D OCT scan over 35°. (c, g) En-face wide-field (35°×35°). (a, e) En-face zoomed-in fundus image of the choroid using 1060nm 3D OCT. Arrows indicate enhanced choroidal visualization. Page 30 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM 3D visualization of volumetric retinal OCT data. Image A shows the whole retinal volume. Image B shows the left part of the volume removed by XZ clipping plane. Image C shows the left part of the volume removed by YZ clipping plane. Image D shows a segmented region of the volume. Page 31 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Top – Spectral OCT image of scan through the fovea of normal retina, rendered in false color. Bottom -- High-magnification, 3D-reconstruction (from individual 2D scans like the one above) of the central retina, showing the foveal “pit.” Page 32 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Retinal Detachments: Embryologically, the inner, “neural” layers of the retina and its outer “epithelial” layer (RPE) are derived from the inner and outer layers of the invaginated optic cup, respectively. During development, the primitive space that lies between these two layers ultimately disappears. However, the legacy of this intraretinal space remains -- the interface between the neural retinal and the RPE is tenuous even into adulthood. Although normally only a potential space, the subretinal space can reappear as a result of the accumulation of fluid between the retina and the RPE. When this occurs, the retina “detaches” from the RPE. The contributing factors to retinal detachment are many. They include trauma to the eye, physical traction on the inner surface of the retina (pulling it away from the RPE) as well as edema caused by the seepage of fluid (e.g., blood, exudates) into the intraretinal space. Page 33 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Page 34 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Retinal Hemorrhages and Exudates: Aspects of retinal anatomy determine the ophthalmoscopic appearance of a retinal hemorrhage or exudate (fluid that has filtered from a blood vessel into the retina). Thus the appearance of a hemorrhage or an exudate is a clue as to its retinal location. Since the NFL is oriented parallel to the ILM, hemorrhages in this layer appear to be “flame-shaped” ophthalmoscopically. Since the “grain” of the deeper retinal layers is oriented perpendicular to the ILM, hemorrhages in these layers (e.g., (IPL, INL, OPL, ONL) are seen “end-on” and appear to be “dots.” Exudates typically accumulate and diffuse in the OPL, especially in the macula, and they have a more amorphous appearance (e.g., clumped, cloud-like). Page 35 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Retinal Signs of Systemic Hypertension: Chronically elevated systemic blood pressure may cause the walls of the retinal arterioles to thicken, resulting in a narrowing of their lumina. These sclerotic arterioles may compress the softer veins wherever they cross over them. Exudates, produced by damaged retinal vessels, may accumulate in the OPL Page 36 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Drusen: Material sometimes accumulates within Bruch’s membrane, pushing the photoreceptors inward, away from the choriocapillaris. The nature of this material (e.g., proteins, lipids) and its appearance (e.g., yellow, white) varies according to the condition causing it to form. The local aggregations can have borders that are sharply delineated (“hard or calcified”) or more diffuse (“soft”), but in each case they are called drusen. Drusen that are numerous and spread over a region of the retinal are said to be “confluent.” If a druse becomes large, the overlying photoreceptors can degenerate, causing a loss of vision. Fundus image showing soft and hard drusen. Histological image of a druse (a) in Bruch’s membrane from older eye. (b) shows age-related accumulation of dense material in Bruch’s membrane. Note RPE disruption above the druse. Page 37 of 38 R.C. V AN S LUYTERS VS 206D F ALL 2010 N EUROANATOMY / PHYSIOLOGY OF THE E YE & V ISUAL S YSTEM Fundus photograph of soft, confluent drusen in an older eye. Page 38 of 38