CHAPTER 7

Retina and Vitreous

Anatomy and Physiology

EMBRYOLOGY The neuroectodermal monolayered optic vesicle invaginates to form a bilayered optic cup with inferior defect (choroidal fissure that closes at 7 weeks). Neural crest mesenchyme migrates through the choroidal fissure and develops into the hyaloid artery. Early on, the cavity of the optic vesicle is contiguous with the diencephalon via the optic canal, and the outermost layer nuclear zone (later the photoreceptors) have ciliated cells that are continuous with ependymal cells of the third ventricle.

The retinal pigment epithelium (RPE) forms from the outer thinner layer of the optic cup, and the neural layer develops from the inner layer. The anterior one fifth of the inner layer remains as a monolayer along with the pigment layer, extending anteriorly as the ciliary body and posterior iris epithelium. The posterior four fifths of the inner layer proliferates into the outer nuclear and the inner marginal zones. The nuclear zone invades the marginal zone to form the inner and outer neuroblastic layers. The inner neuroblastic layer forms ganglia (first retinal cells to recognizably differentiate), amacrine, and Mu¨ller’s cells. The outer neuroblastic layer gives rise to the horizontal, bipolar, and rod and cone cells by the eighth fetal month.

Macula development begins just after midterm, with an increase in the

number of ganglion cell nuclei that begin lateral displacement by 7 months, leaving a fovea centralis. The cones decrease in width and increase in density but are not fully developed until 3 to 4 months after birth.

VASCULATURE Retinal inner three fifths is supplied by branches from the central retinal artery (cilioretinal artery from choroidal circulation present in 20%) and the outer two fifths from choroidal circulation. Central retinal artery pressure ¼ 80/40 mmHg. Retinal veins drain to the central retinal vein, and vortex veins drain to the superior ophthalmic vein, then into the cavernous sinus. Retinal vein at disk ¼ 125 mm wide; 80% of the population has spontaneous venous pulsations.

Choroid is vascularized by two posterior ciliary arteries, supplying the lateral and medial choroid. Thus, a vertical line through the disk is a watershed zone for choroidal infarction. Choroid is vascularized in inner half only.

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220 RETINA AND VITREOUS

Blood–retinal barrier: formed by tight junctions of retinal blood vessels, RPE tight junctions; the internal limiting membrane (BM of Mu¨ller’s cells) protects retina from vitreous.

VITREOUS Composed of hyaluronic acid (secreted mostly from nonpigmented pars plana epithelium) and thin collagen fibrils from hyalocytes. Volume about 4 mL (1 teaspoon). The strongest attachment of the vitreous framework is to the pars plana and around blood vessels and somewhat less around the macula.

Berger’s space is an area between the anterior vitreous (anterior hyaloid face) and the posterior lens capsule. Weigert’s ligament (hyaloideocapsular ligament) is the firm attachment between the anterior hyaloid and the posterior lens capsule. The Weiss ring is the posterior vitreous detachment from the optic disk that floats in the prepapillary space of Mortegiani. Another anatomic space between the vitreous and the retina exists in the premacular bursa.

In infancy, the primary vitreous is mesenchymal vascularized tissue from ectoderm, mesoderm, and neuroectoderm. The secondary adult vitreous is secreted by the retina and Mu¨ller’s cells and thus is of neuroectodermal origin. Finally, the tertiary vitreous comprises the zonules derived from ciliary epithelium.

With age (and accelerated in high myopes, postsurgical, hereditary vitreoretinopathies), liquefaction pockets develop within the vitreous cavity and vitreous fibrils conglutinate, causing floaters. Eventually the internal collapse of the vitreous structure may cause a posterior vitreous detachment (PVD).

RETINAL PERIPHERY The vitreous base inserts 2 mm onto the ora serrata anteriorly and posteriorly 4 mm onto the retina. The posterior base is the main origin of tears, as radial collagen fibers insert perpendicularly into the retina.

Ora serrata: scalloped edge of approximately 48 dentate processes and ora bays.

Enclosed ora bays: may give appearance of retinal hole; may tear at posterior margin after PVD.

Meridional fold: ridgelike elevation of retina perpendicular to the ora in the meridian of ciliary processes, lies partly across the pars plana.

Meridional complex: large dentate process, with occasional thinning posterior to the ridge; completely crosses pars plana.

Cystic retinal tuft: white vitreoretinal mound; may cause up to 10% of RDs.

Ora serrata pearls: small basement membrane material at the ora; not clinically significant, but may be confused for small RB in children. Present in 20% of autopsy eyes.

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White without pressure: posterior extension of vitreous base, especially temporally and in darkly pigmented and myopic patients; does not predispose to RD.

RETINA LAYERS (Fig. 7–1) At the posterior pole retina is 0.5 mm thick (choroid 0.4 mm and sclera 1 mm).

Inner limiting membrane: BM of Mu¨ller’s cells

Nerve fiber layer: axons of ganglion cells; site of juvenile retinoschisis and flame hemorrhages.

Ganglion cell layer: projects via the NFL to lateral geniculate and pretectal nuclei.

Figure 7–1 Simplified schema of the histologic layers of the retina and its cellular components.

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222 RETINA AND VITREOUS

Inner plexiform layer: bipolar-ganglion cell and bipolar-amacrine cell synapses

Inner nuclear layer: Mu¨ller, horizontal, bipolar, and amacrine cell bodies. Approximate limit of retinal circulation (outer retina supplied by the choroid).

Middle limiting membrane (histological artifact)

Outer plexiform layer: site of photoreceptor-bipolar and bipolarhorizontal cell synapses. Also site of CME (cystic spaces from the radiating fibers of Henle), cystoid degeneration, typical degenerative retinoschisis, and lipoprotein exudates.

Outer nuclear layer: rod and cone nuclei

Outer limiting membrane: not a true membrane, but the cell junction of photoreceptors.

Photoreceptor layer: cell bodies of rods and cones

NEUROGLIA Astrocytes (provides structural and metabolic support, proliferates to gliosis), microglial (phagocytosis) and Mu¨ller’s cells (modified astrocytes). Mu¨ller’s cells contain abundant smooth endoplasmic reticulum for detoxification (like hepatocytes and lipid-secreting cells, such as meibomian and adrenal cells), and it traverses the full thickness of the retina; the outer portion scars down to RPE with photocoagulation.

PHOTORECEPTORS (Fig. 7–2) 130 million photoreceptors in the human retina, and the majority are rods (rods:cones ratio ¼ 13:1). Rods function best in dim illumination, with maximum sensitivity at 504 nm (dark adapted). Cones work best in bright light and for color vision, with maximum sensitivity at 555 nm (light adapted). Purkinje’s shift describes adaptation from dark to light. Four visual pigment proteins have considerable sequence homology: the red and green genes found on X chromosome, the blue gene on chromosome 7, and rhodopsin on chromosome 3.

Cones: the human eye has twice as many red cones as green and only 10 to 20% blue. The blue cones are sensitive at 420–445 nm (yellow adapting field), green at 530–545 nm (purple adapting field), and red at 560–575 nm (blue-green adapting field).

Inner synaptic body is the pedicle and may connect with other rods and cones or horizontal and bipolar cells. The inner segment consists of conical inner myoid and outer ellipsoid elements.

The outer segment is a ‘‘9 þ 0’’ cilium (vs. ‘‘9 þ 2’’ in motile cilia) containing stacked laminated disks that are attached to the cell membrane.

Rods: major protein in the outer segments is rhodopsin and consistency is liquid (like olive oil). Spectral absorption peaks arise from different opsin structures and interactions with the chromophore.

The inner synaptic body is the spherule connecting to two horizontal cells or one or more bipolar cells. The inner segment

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Figure 7–2 Diagram of the visual retinoid cycle in the rod photoreceptor outer segment and retinal pigment epithelium. In cones, the chromophore, 11-cis- retinal, is bound to one of three color-sensitive visual pigments instead of opsin. IRBP, intraretinal binding protein; LRAT, lecithin-retinol acyltransferase.

consists of heavily glycogenated inner myoid element next to the cell nucleus and the outer ellipsoid segment containing many mitochondria.

The outer segment is a ‘‘9 þ 0’’ cilium containing multiple, stacked, and separated laminated disks.

The RPE phagocytizes rod outer segment tips that are shed daily 1.5 hours after light onset (diurnal rhythm) and renewed every 10 days (dark deprivation will quickly cease normal rod disk shedding).

Phototransduction cascade: protein photopigment opsin is linked to 11-cis-retinal, which is the chromophore for all photoreceptors. It is a

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224 RETINA AND VITREOUS

derivative of vitamin A, and is aligned parallel to the outer segment disk. The chromophore is isomerized by absorption of a photon to the all-trans configuration and triggers the amplification cascade, beginning with activation of transducin to activate the outer segment cyclic guanosine monophosphate (cGMP) phosphodiesterase. This results in a decrease in cGMP levels, which close cGMP-gated membrane cation channels and thus decrease permeability to sodium, with a resultant fall in intracellular free calcium. This causes hyperpolarization of the photoreceptor membrane (ERG A-wave). The all-trans configuration is oxidized by nicotinamide-adenine dinucleotide phosphate (NADPH) to all-trans-retinol that crosses the membrane to the RPE.

RETINAL PIGMENT EPITHELIUM (RPE) Has an apical-apical arrangement with photoreceptors, and the basement membrane is the internal layer of Bruch’s membrane. Its desmosomes and tight junctions provide the outer blood–retinal barrier. It is the only pigmented monolayer in the eye (CB is a bilayer, but only one layer is pigmented). Its primary function is heat transfer, along with many other metabolic functions in support of the retina, such as storage of vitamin A. With injury, it is a very reactive tissue. Chorioretinal scar is formed from RPE metaplasia and may recruit Mu¨ller’s cells to help with repairs.

BRUCH’S MEMBRANE 2–4 mm thick, composed of five layers: RPE BM, collagen, elastic tissue, collagen, and choriocapillaris BM. Site of angioid streaks and drusen (metabolic wastes possibly from phlebosclerosis, causing malnutrition of overlying RPE and retina).

CHOROID Uveal tissue that is the most richly vascularized tissue per gram in the body and is contiguous with the pia of the ON. The innermost layer is choriocapillaris that arises from the short posterior ciliary arteries; it is expansile and radiator-like, with endothelial fenestrations that allow large molecules (e.g., fluorescein) to leak. Outer lamina fusca pigmented cells adhere to the sclera but detach in choroidal effusions. It does not scar with inflammation; thus, following choroiditis, bare sclera are usually seen as punched-out white lesions. Peripheral choroidal lobule arteriole infarction is seen as paving-stone degeneration. Choroid has an increased number of melanocytes with racial pigmentation (unlike skin and conjunctiva, which only have an increased number of melanosomes within the melanocytes). No lymphatics (thus, ocular Kaposi’s sarcoma is only in the conjunctiva or eyelid).

ANATOMIC DIVISIONS OF THE RETINA

Foveola: central 1.2 degrees, rod-free zone. Umbo has only cones and ILM.

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