Two distinct layers form the inner lining of the posterior two-thirds of the globe:
The neurosensory retina is considered part of the central nervous system (CNS). It is continuous anteriorly with the nonpigmented ciliary epithelium, whereas the RPE is continuous with the pigmented ciliary epithelium. The RPE terminates posteriorly at the optic nerve head, along with the underlying Bruch membrane. The nuclear, photoreceptor, and synaptic layers of the neurosensory retina gradually taper at the optic nerve head, and only the nerve fiber layer (NFL) continues to become the optic nerve, making a 90° turn posteriorly as it becomes the optic nerve head (optic disc). See BCSC Section 2, Fundamentals and Principles of Ophthalmology, and Section 12, Retina and Vitreous, for additional information on the anatomy of the retina and RPE.
The neurosensory retina has 9 distinct histologic layers (Fig 11-1). An additional layer, the middle limiting membrane (MLM), has been described, but it is not a distinct layer on routine histologic sections of the neurosensory retina. On optical coherence tomography (OCT), the photoreceptor inner segment layer appears as several layers because of its innate optical properties: the myoid zone (MZ), which is just external to the external limiting membrane; the ellipsoid zone (EZ), which is closest to the outer segments; and the interdigitation zone (IZ), which is between the outer segments and the RPE (Fig 11-2). The myoid zone contains ribosomes, endoplasmic reticulum, and Golgi bodies, whereas the ellipsoid zone is densely packed with mitochondria of the photoreceptors. In histologic cross sections of the neurosensory retina, the retinal fibers and synaptic processes are arranged perpendicular to the retinal surface, with the exception of the NFL, where the axons run parallel to the retinal surface and converge at the optic nerve head. Consequently, deposits and hemorrhages in the deep retinal layers have a round appearance clinically as they displace the perpendicularly arranged fibers, whereas those in the NFL have a feathery or splinter-shaped appearance (Video 11-1).
Appearance of blood in various retinal layers.
Developed by Vivian Lee, MD.
Go to www.aao.org/bcscvideo_section04 to access all videos in Section 4.
Figure 11-1 Photomicrographs illustrating retinal organization and how it differs depending on location. A, Macula, from vitreous (top of photo) to choroid (bottom): ILM = internal limiting membrane; NFL = nerve fiber layer; GCL = ganglion cell layer (asterisk); IPL = inner plexiform layer; INL = inner nuclear layer; OPL = outer plexiform layer; ONL = outer nuclear layer; ELM = external limiting membrane; P = photoreceptors (inner/outer segments) of rods and cones; RPE = retinal pigment epithelium; Bruch membrane (arrowhead).B, Retina peripheral to the major vascular arcades and posterior to the equator (near-peripheral retina). The asterisk denotes the GCL. C, Retina in the equatorial region. The asterisk denotes the GCL. D, Far-peripheral retina near the ora serrata. Note the reduced density of the GCL (asterisk) and overall thinning of the inner retinal layers. E, In the region of the foveola, the inner cellular layers taper off (right side of photo), with increased density of pigment in the RPE. The incident light falls directly on the photoreceptor outer segments, reducing the potential for distortion of light by overlying tissue elements. Note the multilayered GCL (asterisk), typical of the macula. The OPL fibers travel obliquely in the fovea (Henle fiber layer), and the photoreceptor layer in the fovea consists only of cones.
(Part A courtesy of Robert H. Rosa Jr, MD; parts B–D courtesy of Vivian Lee, MD; part E courtesy of Nasreen A. Syed, MD.)
The morphology of the retina varies depending on the region. For example, histologically, the macula is the area of the retina where the ganglion cell layer (GCL) is thicker than a single cell (see Fig 11-1A). Clinically, this area corresponds approximately with the area of the retina bounded by the inferior and superior major temporal vascular arcades. The center of the macula is further subdivided into the fovea, the central 1.5 mm of the macula, and the foveola, a small pit in the center of the fovea. The foveola contains only cone photoreceptor cells; ganglion cells, other nucleated cells (including Müller cells), and blood vessels are not present (see Fig 11-1E). The concentration of cones is greater in the macula than in the peripheral retina, and only cones are present in the fovea.
Figure 11-2 Macula. A, The normal macula is identified histologically by a thick, multilayered GCL and a central area of focal thinning, the foveola. Note the NFL (arrowhead) in the nasal macular region and the oblique orientation of Henle fiber layer (perifoveal OPL) (asterisk). Clinically, the macula lies between the inferior and superior temporal vascular arcades. B, Spectral-domain optical coherence tomography (SD-OCT) of the macula shows in vivo imaging with high-resolution details of the lamellar architecture of the retina. Note the NFL (arrowhead) in the nasal macular region, Henle fiber layer (asterisk), and the ELM (arrow).C, Higher magnification of the photomicrograph shown in part A and the SD-OCT image shown in part B illustrating the corresponding macular layers. D, SD-OCT image of the macula. NFL = nerve fiber layer; GCL = ganglion cell layer; IPL = inner plexiform layer; INL = inner nuclear layer; OPL = outer plexiform layer; ONL = outer nuclear layer; ELM = external limiting membrane; MZ = myoid zone; EZ = ellipsoid zone; OS = outer segments; IZ = interdigitation zone between outer segments and RPE; RPE/BM = retinal pigment epithelium/Bruch membrane; CC = choriocapillaris.
(Part B courtesy of Robert H. Rosa Jr, MD; parts C (right) and D adapted from Staurenghi G, Sadda S, Chakravarthy U, Spaide RF; International Nomenclature for Optical Coherence Tomography (IN-OCT) Panel. Proposed lexicon for anatomic landmarks in normal posterior segment spectral-domain optical coherence tomography: the IN-OCT consensus. Ophthalmology. 2014;121(8):1572–1578.)
In the outer plexiform layer (OPL) of the fovea (Henle fiber layer), nerve fibers run obliquely (Video 11-2; see also Figs 11-1E, 11-2A). This morphological feature results in the “flower petal” appearance of cystoid macular edema (CME) on fluorescein angiography (FA), as well as the star-shaped configuration of hard exudates observed ophthalmoscopically in conditions that cause macular edema. Xanthophyll pigment gives the macula its yellow appearance clinically and grossly (macula lutea), but the xanthophyll dissolves during tissue processing and is not present in histologic sections. For more on the macula, see Table 1-1 in BCSC Section 12, Retina and Vitreous.
Foveal architecture and related pathologies.
Developed by Vivian Lee, MD.
Outside the macula, the GCL consists of a single layer of ganglion cells and astrocytes. The NFL progressively thins moving anteriorly toward the ora serrata from the optic nerve head. In addition, the most peripheral retina near the ora serrata may lack some of the 9 histologic neurosensory layers (see Fig 11-1B-D).
Two vascular sources supply the retina with some overlap (watershed zone) in the inner nuclear layer (INL). The retinal blood vessels supply the NFL, GCL, inner plexiform layer (IPL), and inner portion of the INL. The choroidal vasculature, specifically the choriocapillaris, which is derived from the posterior ciliary arteries, supplies the outer layers of the retina; these include the outer portion of the INL, OPL, outer nuclear layer, photoreceptors, and RPE. The venous network in these layers drains into the vortex veins.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.