Estratto Ophthalmology Up-To-Date

President

Leonardo Mastropasqua

OPHTHALMOLOGY

UP-TO-DATE

VOLUME 1

Board Members

Aragona Pasquale – Bonini Stefano – Boscia Francesco – Donati Simone

Fontana Luigi – Gandolfi Stefano – Manni Gianluca – Marchini Giorgio

Miglior Stefano – Nardi Marco – Nicolò Massimo – Nucci Paolo

Staurenghi Giovanni – Tognetto Daniele – Vinciguerra Paolo

Fabiano Gruppo Editoriale

Società Oftalmologi Universitari

President

Leonardo Mastropasqua

OPHTHALMOLOGY UP-TO-DATE

VOLUME 1

Board Members

Aragona Pasquale – Bonini Stefano – Boscia Francesco – Donati Simone

Fontana Luigi – Gandolfi Stefano – Manni Gianluca – Marchini Giorgio

Miglior Stefano – Nardi Marco – Nicolò Massimo – Nucci Paolo

Staurenghi Giovanni – Tognetto Daniele – Vinciguerra Paolo

Chapter Editors

G. Alessio

P. Aragona

S. Bonini

M. Busin

C. Cagini

G.M. Cavallini

M. Ciancaglini

C. Costagliola

S. Donati

M. Fossarello

C. Iaculli

A. Lambiase

G. Manni

G. Marchini

L. Mastropasqua

E. Midena

S. Miglior

C. Nucci

P. Nucci

M. Nubile

A. Pinna

P. Rama

L. Rossetti

V. Scorcia

P. Vinciguerra

Fabiano Gruppo Editoriale

© Copyright 2023

Publisher: FGE srl - Fabiano Gruppo Editoriale

Editorial office: Strada 4 Milano Fiori, Palazzo Q7 – 20089 Rozzano (MI) – Italy

Ph. +39 0141 1706694 – info@fgeditore.it – www.fgeditore.it

Printing: FGE srl - Fabiano Gruppo Editoriale

This publication was made possible due to the contribution of:

The Authors and the Editor decline any responsability for any errors in the text. All rights reserved. Reproduction of this book - total or partial - is strictly forbidden.

ISBN 978-88-31256-57-5

Printed in: July 2023

It is with great pleasure and honor that I present, on behalf of the Board Members, the first edition of the Ophthalmology Up-To-Date Textbook edited by the University Italian Society of Ophthalmology (SOU). The aspiration of this book is to be a repository of knowledge and provide doctors with an up-to-date, organized and systematic approach to the visual system. This opera is thought to be useful in the daily practice of any ophthalmologist, but also to act as a guide for the general learning of the young ophthalmologists and trainees. The text is supported by a rich iconography with essential bibliography for further insights, and each chapter provides both basic descriptions and more in-detail knowledge in the various topics treated throughout the book. This publication is divided into three compact but complete volumes that will covering the majority of routine ophthalmological practice. In this first volume, dedicated to the dissertation of clinical pathologies, the different sections will be focused on the “Basics in ophthalmology” (from the anatomy of the eye to clinical refraction), “Diseases of the external eye and orbit”, “Pathologies of the anterior segment of the eye” and “Glaucoma and diseases of the uveal tract”. In the following volume the “diseases affecting the posterior segment of the eye”, “pediatric-and neuro-ophthalmology”, “genetic diseases, ocular oncology and correlations between systemic disorders and the eye” will be covered. The last volume of the opera will be dedicated to a complete description of “Instrumental diagnosis, imaging and technology in ophthalmology” and will contain specific and vast sections dedicated to therapeutics including “Laser and surgical procedures in ophthalmology”. It is belief of all the Authors, whom I personally thank for the great effort and work done in producing the chapters of this textbook, that these three volumes can provide an excellent study basis for ophthalmologists in training, (and also for the most experienced doctors) integrating their learning and skills during the clinical work and the surgical experiences, always suggesting to update their knowledge with the essential study of recent research papers and review monographs. I hope that the readers will enjoy and be stimulated by our ophthalmology textbook.

Leonardo Mastropasqua

VOLUME 1

L. Agnifili

V. Albano

G.M. Bacci

G. Bagetta

A. Borgia

L. Brescia

A. Bruscolini

M. Buzzi

R. Caputo

L. Cerino

F. Chemello

A. Di Zazzo

G. Ferrari

V. Ferraro

F. Formenti

A. Fumagalli

Contributors

G. Gaggiotti

V. Gatti

S. Giammaria

G. Giannaccare

R. Gioia

F. Giovannetti

L. Inferrera

K.A. Knutsson

A. Licata

F. Mallone

A. Meduri

G. Monsellato

R. Morbio

L. Morrone

A. Nuzzi

G. Oliverio

TABLE OF CONTENTS

Section 1 Basics in ophthalmology

Section 2 Diseases of the external eye and orbit

Section 3 Diseases of the anterior segment of the eye

Section 4 Glaucoma and diseases of the uveal tract

VOLUME 2 Next publishing

Section 5 Vitreous and retina

Section 6 Neuro-ophthalmology, pediatrics and injuries

Section 7 Genetic diseases and neoplasia of the eye

Volume 3 Next publishing

L. Pagano

A. Palamini

E. Postorino

D. Rastelli

A. Rodella

D. Romano

M.L. Ruggeri

R. Russo

M. Sacchetti

M. Sacchi

A. Satriano

I. Testi

D. Tomaselli

M. Totta

F. Tranfa

T. Verdina

Section 8 Instrumental diagnosis, imaging and technology in ophthalmology

Section 9 Ocular therapeutics, lasers and surgery in ophthalmology

Basics

Section

Section 1

Anatomy and development of the eye

M. Fossarello

ANATOMY OF THE EYE

Classically the ocular globe is described as a trilaminar structure, which comprises an outer collagenous coat, a middle vascular coat, and an inner nervous coat, and is divided in three chambers, the anterior, posterior, and vitreous chamber [1] (Fig. 1). Moreover, the interior of the ocular globe can be conveniently subdivided into the anterior and posterior segments. The anterior segment includes the cornea, iris, ciliary body and lens, as well as the spaces of the anterior and posterior chambers filled with aqueous humor. The posterior segment includes the retina, choroid and optic nerve head, as well as the vitreous compartment filled with vitreous humor.

Figure 1. The structure of the eye: horizontal cross section through the fovea and optic papilla

The collagenous coat

The collagenous coat is a dense, strong wall protecting the intraocular contents. The anterior 1/6th of this coat is transparent, and represents the cornea; the posterior 5/6 is opaque, and represents the sclera. The junction of the cornea and sclera is known as the limbus. On the inner surface of the limbus there is an indentation, the scleral sulcus, which hosts the trabecular meshwork, a filtering structure essential to regulate the aqueous outflow. The sulcus has a sharp posterior margin, the scleral spur, and an inclined anterior border extending to the peripheral cornea.

The anterior part of the sclera is covered by a mucous membrane, the conjunctiva, which is reflected from its surface onto the lids, forming the conjunctival fornices.

The sclera varies in thickness. It is thin at the insertion of the rectus muscles (0,3 mm), it increases in thickness to about 1 mm posteriorly, and then becomes thin and sieve-like at the lamina cribrosa, where the axons of the retinal ganglion cells exit and form the optic nerve. The cornea measures 12 mm in the horizontal meridian and 11 mm in the vertical meridian, it is thinner ( ̴540 µm) in the center than in periphery ( ̴1000 µm) and is made up of cellular and acellular components, such as epithelial cells, keratocytes, and endothelial cells, and collagen and glycosaminoglycans, respectively. The epithelial cells are derived from epidermal ectoderm.

The cornea is classically subdivided into five layers: the epithelium, Bowman’s membrane, the stroma, Descemet’s membrane, and the endothelium (Fig. 2). Recently, a sixth layer has been described: the Dua’s layer or pre-Descemet layer, a tough collagen layer about 10 μm to 15 μm thick, located between the stroma and the Descemet’s membrane [2] .

The corneal epithelium is composed of nonkeratinized, stratified squamous epithelium, and may be considered as a continuation of the conjunctiva over the cornea. Bowman’s membrane is 8÷14 µm in thickness. It consists of randomly dispersed collagen fibrils merging with the anterior stroma. The stroma is the thickest layer of the cornea and is formed by keratocytes and about 300 collagen lamellae which are regularly arranged to permit corneal transparency. The Descemet’s membrane is a thin, elastic membrane, measuring 10÷12 µm in

Figure 2. Anatomical layers of the cornea. BL, Bowman layer; DM, Descemet membrane; PDL, pre-Descemet layer

thickness, and is the basement membrane of the corneal endothelium. The corneal endothelium is a simple, squamous epithelial sheet on the posterior side of the cornea, serving as a barrier to aqueous humor.

With the exception of minute, approximately 1 mm broad arcades at the limbus, the cornea is avascular and depends for its nourishment upon diffusion of fluid from the vessels at its periphery. It is very richly supplied with nerve fibers derived from the trigeminal nerve (5th branch).

The anterior surface of the cornea is covered by the tear film, which is composed of three layers: (1) a superficial sebaceous layer produced predominantly by modified sweat glands: the Meibomian glands, located in the tarsal plate, and the glands of Moll and Zeis located on the margin of eyelids, (2) a middle watery layer produced by accessory lacrimal tissue and the lacrimal glands, and (3) a deep mucous layer derived from goblet cell secretion within the conjunctiva.

The vascular coat

The vascular coat is called uvea. It is heavily pigmented, and supplies nutrition to the various structures of the eyeball. The uvea consists of three parts, from anterior to posterior, which are: iris, ciliary body and choroid. The choroid and ciliary body line the sclera, while the iris forms a circular diaphragm on the coronal plane, with a central aperture: The pupil

The iris is composed of a stroma containing branched connective tissue cells, with a rich supply of blood vessels which run in a general radial direction. It is usually pigmented in brown irides, and largely unpigmented in blue irides. The stroma is covered with two layers of pigmented epithelium on its posterior surface, which developmentally are derived from the retina. The anterior layer is continuous with the outer layer in the ciliary body and with the pigment epithelium of the retina, while the posterior layer is continuous with the inner unpigmented layer of the ciliary body and with the neuroretina at the ora serrata.

The anterior layer consists of flattened cells, the posterior of cubical cells, and from the epithelial cells of the former two unstriped muscles are developed which control the movements of the pupil, the sphincter pupillae, a circular bundle running around the pupillary margin, and the dilatator pupillae, arranged radially near the root of the iris, where the tissue is thinnest at its attachment to the ciliary body.

The anterior surface of the iris is covered with a single layer of endothelium, except at some minute depressions, or crypts, which are found mainly at the ciliary border.

The iris is rich in sensory nerve fibers derived from the trigeminal nerve. The sphincter pupillae has motor nerve fibers derived from the oculomotor nerve, whilst the motor fibers of the dilatator muscle are derived from the cervical sympathetic chain.

The ciliary body is a triangular structure 6 to 7 mm wide. The anterior surface forms part of the angle of the anterior chamber and continues anteriorly to form the uveal trabecular meshwork and the root of the iris; posteriorly, it gradually forms a continuum with the choroid. The ciliary body has two principal functions: 1) aqueous humor formation, and 2) accommodation.

The ciliary body can be divided into two parts: the ciliary muscle, and the ciliary epithelium and stroma (Fig. 3).

The ciliary muscle is composed of unstriped muscle fibers and is generally subdivided into three parts: 1) the meridional or longitudinal muscle externally; 2) the circular or radial muscle internally; and 3) a variable oblique muscle in between. All three share a common origin in the ciliary tendon, a structure which runs circumferentially around the globe blending with the spur of the sclera and related to the corneo-scleral trabeculae. The greater part of the muscle is composed of meridional fibers running antero-posteriorly on the inner aspect of

the sclera to find a diffuse insertion into the suprachoroid. Most of the remainder of the fibers run so obliquely in interdigitating V-shaped bundles as to give the impression of running in a circle round the ciliary body concentrically with the base of the iris. The third portion of the muscle is composed of a few tenuous iridic fibers arising most internally from the common origin and finding insertion in the root of the iris, just anterior to the pigmentary epithelium in close relation to the dilatator muscle.

The inner surface of the ciliary body is divided into two regions: the anterior part is corrugated with several major folds running in an antero-posterior direction (pars plicata), while the posterior part is smooth (pars plana).

The pars plicata has about 70 plications around the circumference, the ciliary processes, which contain tufts of blood vessels, similar to glomeruli, supplied by arterioles that originate from the major arterial circle of the iris, and many smaller microscopical crests in the valleys between them, the plicae ciliaris. The zonular fibers of the crystalline lens attach primarily in the valleys of the ciliary processes, but also along the pars plana. The ciliary processes produce the aqueous humor by a combination of diffusion, ultrafiltration of blood, and active secretion by ciliary epithelium into the posterior chamber.

The pars plana (orbiculus ciliaris) is flat, extending for about 4 mm from the posterior edges of the ciliary processes to the ora serrata.

The inner surface of the ciliary body is lined by two layers of epithelium, which belong properly to the retina, and are continuous with the similar layers in the iris. The inner layer is nonpigmented epithelium, and the outer layer is pigmented epithelium, unlike the condition in the iris. The apices of these two cell layers are fused by a complex system of tight junctions

Figure 3. Schematic drawing of the anterior chamber angle.

and cellular interdigitations. Along the lateral intercellular spaces, near the apical border of the nonpigmented epithelium, there are zonulae occludentes which help to maintain the blood-aqueous barrier.

The ciliary body is richly supplied with sensory nerve fibers, derived from the trigeminal nerve. The ciliary muscle is supplied with motor fibers from the oculomotor and sympathetic nerves. The main arterial supply to the ciliary body arises from the long posterior and the anterior ciliary arteries, which come together to form the major arterial circle of the iris, located posterior to the anterior chamber angle recess in the ciliary body. The main venous drainage is posteriorly through the vortex veins, although some drainage also occurs via the intrascleral venous plexus and the episcleral veins in the limbal region.

The choroid is the posterior portion of the uveal tract and is an extremely vascularized membrane in close contact with the sclera, although not firmly adherent to it, so that there is a potential space between the two structures: The epichoroidal space.

On the inner side the choroid is covered by a thin elastic membrane, the lamina vitrea, or membrane of Bruch. The blood vessels of the choroid increase in size from within outwards, so that immediately beneath the membrane of Bruch there is a capillary plexus of fenestrated vessels, the choriocapillaris. The choriocapillaris is structurally a continuous layer of capillaries lying in a single plane beneath the retinal pigment epithelium. The vessel walls are extremely thin and contain multiple fenestrations, especially on the surface facing the retina. Pericytes are located around the outer wall. Following upon there is the layer of medium-sized vessels, while most externally are the large vessels, the whole being held together by a stroma consisting of branched pigmented connective tissue cells. The middle and outer choroidal vessels are not fenestrated.

The choroid is supplied with sensory nerve fibers from the trigeminal nerve, as well as autonomic nerves presumably of vasomotor function.

The nervous coat

The inner nervous coat, called the retina, is located between the choroid and the vitreous, extending from the circular edge of the optic disc, where the nerve fibers exit the eye, to the ora serrata, where is continuous with the double-layered epithelium of the ciliary body and iris. It consists of an outer pigmented layer tightly adherent to the choroid, and of the sensory neural retina.

The neural retina is a light-sensitive, highly complex and specialized tissue, comprised of neural, glial, and vascular elements, and is classically subdivided into nine layers (from vitreal to scleral side): four strata of cells and their synapses (ganglion cell layer, inner nuclear layer, outer nuclear layer, layer of photoreceptors’ outer segments), three strata of axons and dendrites (optic nerve fiber layer, inner plexiform layer, outer plexiform layer) and two limiting membranes (inner and outer). The pigment epithelium represents the tenth layer (Fig. 4). Although it contains millions of cell bodies and their processes, the neural retina has the appearance of a thin, transparent membrane.

The neuronal architecture of retina is developed both horizontally and vertically: the photoreceptors layer is followed by the outer nuclear layer (the nuclei of rods and cones), the outer plexiform layer (comprised of synapses between photoreceptors, bipolar and horizontal cells), the inner nuclear layer (the nuclei of the horizontal, bipolar, and amacrine cells), the inner plexiform layer (comprised of synapses between bipolar, amacrine and ganglion cells), the ganglion cell layer (the nuclei of ganglion cells) and finally the nerve fiber layer composed of the axons of ganglion cells, running centrally to the optic disc, where bend to 90° to cross the lamina cribrosa in the scleral canal and form the optic nerve surrounded by its medullary

sheaths. The ganglion cells axons then partially decussate on contralateral side at the optic chiasm, and with the name of optic tract make synapses mainly with the lateral geniculate nucleus in the thalamus, but for a small part also with the suprachiasmatic nucleus in the hypothalamus, and with the superior colliculus of the midbrain. These special nervous constituents are bound together by neuroglia, the better developed vertical cells being called Müller cells, which in addition to acting as a supportive framework, extending from the inner to the outer limiting membrane, have a nutritive function. The structure is completed by two limiting membranes, the outer perforated by the rods and cones, and the inner separating the retina from the vitreous.

The primary light-sensing cells in the retina are the photoreceptor cells, located more externally, in close contact with the pigment epithelium, which are of two types:  rods and  cones Rods are found concentrated at the outer edges of the retina, while cones are mainly located in the center of the retina, in an area called fovea centralis. Photoreceptors are absent from the optic disc, contributing to the blind spot. On average, there are approximately 120 million rods and six to seven million cones in the human retina.

Photoreceptors can respond to light by virtue of a visual pigment embedded in the membranous discs that make up their outer segment. The visual pigment consists of a protein called opsin and a chromophore derived from vitamin A known as retinal Retinal originates from beta-carotene present in certain foods, while opsin is synthesized in the photoreceptor cells.

Figure 4. Schematic drawing of retinal structure (From Ferrara et al.)[3]

Rods contain the visual pigment rhodopsin and are sensitive to blue-green light with a peak sensitivity around 500 nm wavelength. Rods are highly sensitive photoreceptors and are used for vision under dark-dim conditions at night. Cones contain the visual pigments cone opsins and, depending on the exact structure of the opsin molecule, are maximally sensitive to either long wavelengths of light (red light), medium wavelengths of light (green light) or short wavelengths of light (blue light). Cones are responsible for daytime vision as well as high-acuity vision, and by virtue of their three different wavelength sensitivities, they are the basis of color perception.

The photoreceptor outer segments consist of a cell membrane which encloses a stack of membranous discs. The discs are continuously renewed throughout life with a circadian rhythm. New discs are formed in the region of the inner segment and are progressively displaced towards the tip of the outer segment, to be shed and phagocytized by the pigment epithelium cells. In this way, despite the continuous formation of new discs, the photoreceptors maintain constant axial lengths.

Shed photoreceptor disks bind to the apical RPE surface following light onset and are internalized via a series of phagocytic and endosomal compartments prior to converging with lysosomes for degradation. The major end products of lysosomal enzyme action are lipofuscin granules, autofluorescent particles containing oxidized proteins and lipids, accumulating in an age-related manner in the cytoplasm of RPE cells. Other products are residual bodies, thought to represent incomplete breakdown products of phagolysosomes, and drusen, extracellular excrescences of RPE cells that are common in the elderly population.

A third type of light-sensing cells, the photosensitive ganglion cells, containing melanopsin, are important for entrainment of circadian rhythms and reflexive responses such as the pupillary light reflex.

The micro-anatomy of rods and cones reveals the transductive region (outer segment), a region for the maintenance of cellular homeostasis (inner segment), a nuclear region (outer nuclear layer) and a synaptic transmissive region (the outer plexiform layer). At the junction of the inner and outer segment the cell body constricts due to the presence of a connecting cilium.

The center of the posterior retina may be subdivided topographically into different regions. The  anatomical macula, (also called macula lutea or area centralis) is an oval-shaped pigmented area that contains xanthophyll and two or more layers of ganglion cells, located about 3,5 mm to the temporal side of the optic disc, and may be further subdivided into the umbo, foveola, foveal avascular zone, fovea, parafovea, and perifovea areas. The anatomical macula has a size of 5.5 mm and is much larger than the clinical macula which, at a size of 1.5 mm, corresponds to the anatomical fovea (Fig. 5). The anatomical fovea is a depression in the inner retinal surface, about 1.5 mm wide, and contains only cones for maximum visual acuity.

The retina is thickest at the foveal margin (0.23 mm) and tapers to approximately 0.10 mm at the foveal center (umbo), and 0.18 mm at the equator. It gradually thins further to 0.11 mm in thickness at the ora serrata as the density of all the neuronal elements, including photoreceptors and ganglion cells, decreases peripherally.

The retina is supplied by two vascular systems: the inner portion by blood vessels arising from the central retinal artery, a branch of the ophthalmic artery, originating from the inner carotid artery, and both the retinal pigment epithelium and outer retina by the choriocapillaris (Fig. 6).

The central retinal artery travels along the inferior margin of the optic nerve sheath and then enters the eye through the center of the optic nerve. The artery then branches in the inner

Figure

positions

of the anatomic macula (macula lutea) and clinical macula. The anatomic macula is about 5.5 mm in diameter, is centered approximately 3,5 mm temporal and 0.8 mm inferior to the center of the optic disk and corresponds clinically to the posterior pole. The anatomic fovea (fovea centralis) is an area of depression about 1,5 mm in diameter located in the center of the anatomic macula, and it corresponds to the clinical macula (about 5 degrees of visual field).

5. Schematic diagram showing the

and sizes

Figure 6. Arterial supply to the retina

retina to form three capillary layers: superficial, intermediate, and deep capillary plexus (Fig. 7). There are no blood vessels in the retina at the macula, so that its nourishment is entirely dependent upon the choroid.

The anatomy of retinal circulation has been recently implemented by optical coherence tomography angiography (OCTA) studies [4]

The anterior chamber

The anterior chamber is a space filled with aqueous humor, a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is limited anteriorly by the cornea and posteriorly by the iris and part of the anterior surface of the crystalline lens. The anterior chamber is about 2,5 mm deep in the center in the normal adult, it is shallower in very young children and also in old people. Its peripheral recess is known as the angle of the anterior chamber, bounded posteriorly by the root of the iris and the ciliary body and anteriorly by the corneo-sclera. The trabecular meshwork is located in this area of corneosclera, corresponding topographically to the limbal area. (Fig. 3).

From the anterior chamber the aqueous humor leaves the eye by passive flow via two pathways: The trabecular meshwork (the conventional route) and the uveoscleral pathway (the non-conventional route).

The trabecular meshwork pathway is represented by the three layers of the trabecular meshwork, which drain into the Schlemm’s Canal. The trabecular meshwork is a complex, fenestrated, three-dimensional structure composed of trabeculae interdigitated into a multilayered organization within the extracellular matrix. The meshwork trabeculae consist of an inner core of collagen and elastic fibers embedded in ground substance and covered by basement membrane and endothelium. The endothelial cells are a continuation of the corneal endothelium and contain the cellular organelles for

Figure 7. Location of the vascular plexi (superficial, intermediate and deep) relative to the various cell types that construct the anatomy of the retina

protein synthesis and lysosomes, which give them the capacity for phagocytosis. The trabecular meshwork represents the main pathway for the drainage of aqueous humor out of the eye and is a crucial determinant of intraocular pressure values due to its resistance to outflow of aqueous humor. It is roughly triangular in shape, with the apex bounded by the Schwalbe’s line, and the base formed by the scleral spur and the ciliary body. It can be divided into three layers: the uveal, the corneoscleral meshwork, and the juxtacanalicular tissue adjacent to Schlemm’s canal.

Sympathetic innervation of the trabecular meshwork originates from the superior sympathetic ganglion. Parasympathetic innervation derives from the ciliary ganglion. Sensory nerves originate from the trigeminal ganglion.

The Schlemm’s canal is a modified capillary blood vessel lined by endothelial cells, running parallel to the limbus as a circumferential channel, within the posterior part of the corneoscleral junction. The endothelium of Schlemm’s canal collects the aqueous humor mainly by a specialized form of transcellular transport, represented by the formation of giant vacuolar transcellular channels. From the lumen of Schlemm’s canal the humor aqueous is drained through a system of 25-30 collector channels, into the deep scleral plexus, then into the intrascleral plexus, followed by the episcleral plexus, which in turn opens into the anterior ciliary veins, which finally merge into the ophthalmic veins. A small amount of the collector channels (~10%) bypass the deep scleral plexus and open into the conjunctival veins.

The uveoscleral pathway is composed of the uveal meshwork and anterior face of the ciliary muscle. The aqueous humor enters the connective tissue between the muscle bundles, through the suprachoroidal space, and out through the sclera.

The posterior chamber

The posterior chamber is a narrow space filled with aqueous humor, located behind the peripheral part of the iris, the anterior part of the crystalline lens, the ciliary zonule, and the ciliary processes (Fig. 3). It is an important structure involved in the production and circulation of aqueous humor. The aqueous humor is produced by the epithelium of the ciliary body, from which it flows through the pupil to enter the anterior chamber.

The ciliary zonule (zonule of Zinn or suspensory ligament of lens) is a ring of radially arranged, thread like fibers which anchor the equator of the lens and adjacent anterior and posterior surface of the lens to the ciliary body and ciliary part of the retina. The zonular fibers are separated by two spaces which encircles the equator of the lens, one between the posterior fibers and the anterior surface of the vitreous body (Canal of Petit), and one between the anterior and posterior fibers (canal of Hannover).

The crystalline lens is a transparent mass of peculiarly differentiated epithelium, located behind the iris and in front of the vitreous body, made up mostly of proteins, called crystallins (α,β,γ). The lens has an ellipsoid, biconvex shape, with the anterior surface less curved than the posterior.

The crystalline lens has three main components: the  lens capsule, the lens epithelium, and the lens fibers. The lens capsule forms the outermost layer of the lens, and the lens fibers form the bulk of the interior of the lens. The cells of the lens epithelium, located between the lens capsule and the outermost layer of lens fibers, are found only on the anterior side of the lens. The lens itself lacks nerves, blood vessels, or connective tissue.

The lens capsule is a smooth, transparent basement membrane that completely surrounds the lens. It is synthesized by the lens epithelium and its main components are type IV collagen and sulfated glycosaminoglycans. The capsule is very elastic and so allows the lens

to assume a more spherical shape when not under the tension of the zonular fibers, which connect the lens capsule to the ciliary body. The posterior surface of the lens capsule is in contact with the anterior hyaloid of the vitreous by means of the annular hyaloideocapsular ligament of Weiger, which delimits, a virtual space between the two structures, called patellar fossa, or retrolental space of Berger.

The lens epithelium is a simple cuboidal epithelium, and it is located in the anterior portion of the lens, between the lens capsule and the lens fibers. The cells of the lens epithelium regulate most of the homeostatic functions of the lens. The equatorial cells of the lens epithelium generate the lens fibers in a region referred to as the germinative zone. The lens epithelial cells elongate, lose contact with the capsule and epithelium, synthesize crystallins, and then finally lose their nuclei as they become mature lens fibers. The new fibers are constantly laid down from the embryo age for lifelong growth, with the new secondary fibers being added as outer layers.

The lens fibers form the bulk of the lens. They are long, thin, firmly packed transparent cells, with a diameter of typically 4–7 micrometers and length up to 12 mm, and contain crystallins. They are arranged in concentric layers rather like the layers of an onion. These tightly packed layers of lens fibers are referred to as laminae. The lens fibers are linked together via gap junctions and interdigitations of the cells that resemble “ball and socket” forms. The lens is split into regions depending on the age of the lens fibers of a particular layer. Moving outwards from the central, oldest layer, the lens is split into an embryonic nucleus, the fetal nucleus, the adult nucleus, and the outer cortex.

The vitreous chamber

The retina and the lens delimit externally the vitreous chamber, the largest space of the eye, filled with several milliliters of a highly viscous gel, called the vitreous body (or vitreous humor) (Fig. 1). The structure is composed of a framework of extremely delicate embryonic-like collagen filaments, closely associated with a large quantity of water-binding hyaluronic acid. The rest is a mixture of proteins, salts and sugars. It makes up four-fifths of the volume of the eyeball (~80% of the eye’s volume), and 99% of it consists of water. The vitreous body is fluid-like near the center, and gel-like near the edges. The vitreous body is surrounded by a layer of collagen called the hyaloid membrane (or vitreous membrane or vitreous cortex) separating it from the rest of the eye. The anterior hyaloid is bounded by the posterior surface of the lens, with a reciprocal contact by means of Wieger’s ligament, which delimits a depression called the patellar fossa, or retrolental space of Berger. The lateral hyaloid is bounded at the ora serrata by the internal limiting membrane of the retina and of the posterior pars plana, and the posterior hyaloid by the retinal internal limiting membrane and by the optic disc. Inside the vitreous there is a transparent canal that runs from the optic nerve disc to the lens called Cloquet’s canal, also known as the hyaloid canal, which serves as a perivascular sheath surrounding the hyaloid artery, a prolongation of the central artery of the retina, which supplies blood to the developing lens in the embryonic eye. Moreover, the vitreous presents a system of liquid spaces, the premacular bursa overlying the macula, surrounded by a circle of other liquid-filled spaces termed cisterns [5] The vitreous is firmly attached at the vitreous base located at the ora serrata. Additional firm attachments exist at the optic nerve head, overlying retinal vessels, and near the human fovea.

The vitreous body plays an important role in providing metabolic nutrient requirements of the lens, coordinating eye growth and providing physical support to the retina [6]

OPHTHALMOLOGY UP-TO-DATE

References

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