Ocular Embryology

Ocular Embryology

THE EYE

BASIC ANATOMY AND PHYSIOLOGY

• MOSHI

PREFACE

• This book is written to provide the Assistant Medical Officer-
• Ophthalmology , the Optometrist and the Ophthalmic nurse, with basic
• knowledge of anatomy and physiology of the eye.
• The practical application of anatomic facts to ophthalmology, has been
• emphasised throughout the book. Clinical problems requiring anatomic
• knowledge for their solution, are presented at the end of each chapter.
• Weare greatly indebted to the members of the Advisory Board, Allied
• Health Sciences School KCMC, for their moral and financial support.
• Ophthalmologists

Moshi

CONTENTS

CHAPTER 1:

CHAPTER 2:

CHAPTER 3:

CHAPTER 4:

CHAPTER 5:

CHAPTER 6:

CHAPTER 7:

CHAPTER 8:

CHAPTER 9:

CHAPTER 10:

CHAPTER 11:

CHAPTER 12:

OCULAR EMBRYOLOGY

THE ORBITAL CAVITY

THE EYELIDS

THE LACRIMAL_ APPARATUS

THE EXTRAOQCULAR MUSCLES

THE EYEGLOBE

THE CORNEA AND THE SCLERA

THE ANTERIOR CHAMBER

THE UVEAL TRACT

THE CRYSTALLINE LENS

THE RETINA AND THE VITREOUS

NEURO-OPHTHTALMIC_ ANATOMY

AND PHYSIOLOGY

• 14
• 22
• 27
• 37
• 40
• 46
• 52
• 61
• 67

83

CHAPTER 1.

OCULAR EMBRYOLOGY

• 1. INTRODUCTION.
• Developmentally and functionally the eye is an extention of the central
• nervous system.
• The human eye development commences in the 4" week of gestational age
• and the
• tissues that will constitute the human eye, are derived from:
• e surface ectoderm;
• e neural ectoderm;
• e neural crest;
• mesodermal mesenchyme.
• Embryologic Derivation of Ocular Structures
• Surface ectoderm gives rise to:
• + Lens
• + Corneal epithelium
• + Conjunctival epithelium and lacrimal glands
• + Epithelium of eyelids and cilia, meibomian glands, and
• glands of Zeis and Moll
• + Epithelium lining nasolacrimal system
• Neural ectoderm gives rise to:
• + Retinal pigment epithelium
• + Neural retina
• + Optic nerve fibers
• + Neuroglia
• + Epithelium of ciliary body
• + Epithelium of iris, including iris sphincter and dilator
• muscles
• Neural crest gives rise to:
• + Corneal stroma (which gives rise to Bowman’s layer)
• + Corneal endothelium (which gives rise to Descemet’s
• membrane)
• + Most (or all) of sclera
• + Trabecular structures
• + Uveal pigment cells
• + Uveal connective tissue
• + Vascular pericytes
• During the embryonic development of the eye, the final differentiation and
• sangerent of clare conta by numerous inductive and suppressive
• These interactions are mediated by specific elements; recently, three
• elements have been identified , as making very important contributions to
• the series of sequential events:
• e growth factors;
• ¢ homeobox (homeotic) genes; One particular gene that appears to be
• important in the development of ocular structures is the Pax-6 gene.
• As it influence the development of lens, cornea and conjuctiva
• e neural crest cells.

2. CHRONOLOGY OF OCULAR DEVELOPMENT AND COMMON

DEVELOPMENTAL DISORDERS.

• As stated above, the eye embryologically develops parallel with the central
• nervous system. During the third week of embryonic development, the three
• primary germ layers— ectoderm, mesoderm, and endoderm— have formed
• the embryonic plate.4 (Of
• these three, only ectoderm and mesoderm will take part in the developing
• ocular structures.) A thickening in the ectoderm, visible on the dorsal surface
• of the embryo,
• forms the neural plate, which will give rise to the central nervous system,
• including ocular structures.
• In humans, the central nervous system differentiates from ectoderm.
• First, the neural plate develops (neural ectoderm), then the neural groove
• and the neural folds .
• Later the walls of the groove fuse, forming the neural tube. The developing
• central nervous system is now recognised as the neural tube. The ectoderm
• now lining the tube is neural ectoderm and that surrounding the tube is
• surface ectoderm,
• which differ both in anatomic location and in differentiation potentials
• By day 22 (embryological age) and embryo size 2-3 mm, the optic sulci
• develop on the neural folds; later the sulci become pits, then optic vesicles.
• At the same tim:
• , which contribute extensively to
• the development of the eye. These neural crest cells come to lie between the
• neural tube and the surface ectoderm
• Mery of the neural crest cells migrate away from the neural tube,and form
• Congenital and developmental anomalies that involve cells derived from the
• neural crest have been mer ssaent under the term
• Formed by the deepening of the optic pits, the optic vesicles are continuous
• with the neural tube, by optic stalks ( future optic nerve).The cavity of the
• hollow optic vesicle communicates with that of the forebrain.Later the optic
• vesicle invaginates to form the optic cup with its two layers.
• Optic cup
• Optic stalk
• Surface ectoderm
• Lens vesicle
• Choroid fissure
• Mesectoderm
• (Neural crest)
• Hyaloid
• artery
• Fig. 1.1. Diagrammatic representation of the : optic cup, lens vesicle, optic
• stalk and embryonic ( choroids) fissure.
• At about sper of seit n one te ize 4. it
• Gradually the lens placode invaginates and the lens vesicle is formed ( by day
• 29).

im th 33, the lens vesicle Soar from T_T

OPTIC PITS

• The optic pits form as indentations on both sides of the neural tube in the
• forebrain region even before the tube is completely closed. On
• approximately day 25, after the neural tube has closed, the optic pits form
• lateral sac- shaped extensions, the optic vesicles.
• Neural crest cells and mesoderm collectively make up the mesenchyme, from
• which the connective tissue of the globe and orbit develop. Mesodermal cells
• and neural crest cells appear similar cytologically. If the origin is uncertain,
• mesenchyme is cited as the germ layer. As the optic vesicle evaginates, the
• tissue joining the vesicle to the neural tube constricts, forming the optic
• GD ait with wes offic
• stalk. The cavity of the optic stalk, as well as that of the optic vesicle, is
• continuous with the space that will become the third ventricle. While the
• wall of the optic vesicle is in contact with surface ectoderm, it thickens and
• flattens to form the retinal disc.7 The lower wall of the optic vesicle and
• optic stalk begins to buckle and move inward toward the upper and
• posterior walls. This invagination forms a cleft, variously called the optic
• fissure, embryonic fissure, or fetal fissure.
• 3
• The . The lens
• capsule
• Later, oon lens Prenatal voF onithel -are synthesized
• During embryonic and fetal development the lens receives nourishment via
• an intricate vascular net, the tunica vasculosa lentis.
• The tunica vasculosa lentis is formed by capillaries from the hyaloid artery
• and from the pupillary membrane (the annular artery).
• Primary
• vitreous
• Secondary
• vitreous
• +— Eyelid epidermis
• Conjunctival epithelium
• -Corneal epithelium
• ‘Corneal stroma
• Tunica vasculosa
• lentis
• Fig.1.2. Diagrammatic representation of the tunica vasculosa lentis.
• Normally, the hyaloid system of vessels vanishes completely, but in some
• disorders regression does not occur or it is incomplete;
• Common malformations of the lens are : congenital cataract, microphakia,
• spherophakia.
• Concurrently with the lens vesicle formation, the optic vesicle invaginates
• and develops into the optic cup. The optic cup at this stage of development
• is composed of two layers of cells (both neuroectodermal in origin) that are
• continuous with each other at the rim of the cup. The outer layer of the
• optic cup will become the retinal pigment epithelium (RPE), the outer
• pigmented epithelium of the ciliary body, and the anterior iris epithelium.
• The inner layer will become the neural retina, the inner nonpigmented
• ciliary body epithelium, and the posterior iris epithelium
• The outer layer of the cu
• After week 6 the RPE is one cell thick, the
• At approximately week 7,
• cell migration occurs ayt the inner layer of the optic cup, forming the inner
• and outer neuroblastic layers, between which lies the transient fiber layer of
• Chievitz, a nucleus- free area. Differentiation of the neural retinal cells begins
• in central retina and proceeds to the periphery
• Mesenchymal cells of mesodermal origin penetrate the optic cup through
• the embryonic fissure and presumably contribute to the organisation of the
• During embryologic development, formation and growth of structures
• depend on tissue differentiation. tissues. Some structures will not develop
• unless they are near another developing area at a specific time. There is
• some uncertainty regarding whether the two structures must actually come
• in contact or just be in proximity, but substances must be able to pass
• between them.12 This influence that one developing structure has on
• another is termed induction. It is likely that the mechanism of induction is
• not a single event but a series of separate steps that presumably occur ona
• biochemical level.
• The optic cup and stalk are incomplete inferiourly – there is an embryonic
• fissure
• that extends from the rim of the cup to the optic stalk;
• This fissure allows vessels of the hyaloid system to be incorporated into the
• eye; by the end of the 6" week, the optic fissure starts to fuse .
• Payer or von i closure ingot ——————
• The development of the iris, ciliary body , choroid and anterior chamber
• angle, involves an interaction between mesenchyme and neuroectoderm.
• The smooth muscles of the iris , the sphincter and dilator muscle, are unique
• in embryologic terms as they differenciate directly from neuroectoderm,
• The ciliary muscle, differenciates at around 75 weeks gestation , from the
• mesenchyme of neural crest origin.
• Common developmental disorders of the uvea and angle structures, are:
• aniridia, colobomas, congenital glaucoma.
• cornea
• Corneal genesis is
• The surface ectoderm which seals over the lens pit forms the future corneal
• epithelium, while the stroma and the endothelium originates from neural
• crest derived mesenchyme. By the fifth or sixth month, all the cellular layers
• of the corneal
• epithelium are present. Corneal endothelium, formed from the first wave of
• mesenchyme that migrates into the space between the corneal epithelium
• and the lens,
• is one to two cells thick by week 6. At 4 months the endothelium is a single
• row of flattened cells with a basal lamina, the first evidence of Descemet’s
• membrane. By week 8 a second wave of mesenchyme proliferates and then
• splits. The posterior portion migrates into the area between the developing
• endothelium and lens,
• giving rise to the pupillary membrane. The anterior portion migrates
• between the developing epithelium and endothelium and gives rise to the
• fibroblasts,
• collagen, and ground substance of the stroma. This is second wave
• mesanchyne and it give rise to the sclera. At 3 months all layers of the
• cornea are present except Bowman’s layer, which appears during the fourth
• month and is presumably formed by fibroblasts of the anterior stroma and
• secretions of the epithelial cells
• Developmental anomalies of the cornea include : microcornea, megalocornea,
• sclerocornea, neurocristopathies (i.e. Peter's anomaly, Rieger’s anomaly,
• Axenfeld’s anomaly).
• sclera.
• The sclera is a result of mesenchymal condensation too. During the fourth
• month
• connective tissue fibers cross the scleral foramen,running through the optic
• nerve fibers and producing the first connective tissue strands of the lamina
• cribrosa. By the fifth month the sclera (including the scleral spur) is well
• differentiated
• UVEA
• Choroid.
• The mesenchyme that forms the choriocapillaris must be in contact with the
• developing pigment epithelium to differentiate. During the fifth month the
• layers
• of the large and medium vessels are evident, as are the vessels that will
• become vortex veins. The short posterior ciliary arteries also are evident and
• begin to anastomose to form the circle of Zinn. At midterm in fetal
• development the elastic sheet of Bruch’s membrane is present, the
• basement membrane of the RPE is developing, and the collagenous layers
• are thickening. The basement membrane of the choriocapillaris

is the last component to appear. By term the choroidal stroma is pigmented.

Ciliary Body

• The region of the outer layer of the optic cup, which will become the outer
• pigmented epithelium of the ciliary body, begins to form ridges late in the
• third month. The inner nonpigmented epithelium, from the inner optic cup
• layer, grows and folds with it. These folds, almost 70 in number, become the
• ciliary processes. The ciliary muscle begins to develop during the fifth
• month. However, the annular muscle (of Muller) remains incomplete at
• birth.
• Both epithelial layers begin to produce aqueous humor at 4 to 6 months of
• gestation
• Iris
• By the end of the third month the lip of the optic cup begins to elongate and
• grows between the lens and the developing cornea. The outer layer of the
• optic cup
• becomes the anterior iris epithelium and the inner layer forms the posterior
• iris epithelium. The group of cells that will become the iris sphincter breaks
• away from the pupillary zone of this epithelial layer during the fifth month
• and develops into smooth muscle within the iris stroma. During the sixth
• gestational month the fibers
• of the dilator muscle continue to develop within the epithelial layer, and
• both muscles are completed by birth. That the sphincter and dilator come
• from neural
• ectoderm is unusual, because most muscle tissue is derived from
• mesenchyme. Pigmentation in the anterior and posterior epithelium begins
• to appear at
• approximately week 10 and is complete during the seventh month. A sparse
• distribution of collagen fibers begins to accumulate to form the iris stroma.5
• Stromal melanocytes continue to produce more pigment, and the color of
• the iris can
• continue to darken for the first 6 postnatal months, with some stromal

organization not complete until age 7 years.

PUPILLARY MEMBRANE.

• During the third month the pupillary membrane forms between the lens
• epithelium and the corneal endothelium to replace the vascular tunic. This
• transitory membrane has components from the second wave of
• mesenchyme and branches from the major circle of the iris. The vessels of
• the pupillary membrane cannot be identified as arterial or venous on the

basis of their histologic makeup.

ANTERIOR CHAMBER.

• A mass of cells of neural crest origin and from the first wave of mesenchyme
• accumulates adjacent to the ciliary body and the iris root in the anterior
• chamber angle
• Area. The trabecular meshwork is visible as a triangular mass of
• mesenchymal cells during the fourth month; at least part of this tissue is of
• neural crest origin. Schlemm’s canal is derived from the deep scleral plexus.
• Once formed, the anterior chamber is lined by a continuous endothelium

that covers the trabecular meshwork and the iridocorneal angle.

VITREOUS

• The presence of the developing lens is essential for normal accumulation of
• vitreous.
• The primary vitreous fills the vitreous space early in development and is
• made up of fibrils derived from the developing lens, the developing retina,
• and the degenerating hyaloid system. As the secondary vitreous develops,
• apparently produced by the neural retina and hyalocytes from the primary
• vitreous,1 it encloses the primary vitreous in the region of the atrophying
• hyaloid vessels, thus forming the funnel- shaped Cloquet’s canal. The
• secondary vitreous contains a fibril network and primitive hyalocytes. The
• zonule fibers develop from the tertiary vitreous, located between the lens

equator and the ciliary body.

OPTIC NERVE

• The optic stalk, the precursor of the optic nerve, joins the optic vesicle to the
• forebrain. As the optic fissure develops along the inferior stalk invagination,
• atwolayered optic stalk is created. The outer /ayer of the optic stalk
• becomes the neuroglial sheath that surrounds the optic nerve; it also gives
• rise to the glial components of the lamina cribrosa. Programmed cell death
• occurs in the cells of the inner /ayer, providing an avenue for passage of the
• axons from ganglion cells entering the optic stalk; other cells of the inner

wall become the glial cells of the optic nerve.

DEVELOPMENT OF OCULAR ADNEXA.

• Periocular tissues ( bones, cartilage, fat, connective tissues of the orbit ),
• originate from thelineural cresticells/of the frontonasalland maxillary
• processesOrbitalifat and connective tissue are derived from neural crest
• cells. The first evident orbital bone is the maxilla at 6 weeks; the frontal,
• zygomatic, and palatine bones are apparent at week 7. The lesser wing of the
• sphenoid bone and the optic canal are present at week 7, the greater wing is
• evident at week 10, and the wings join at week 16. The angle
• between the orbits early in development is approximately 180 degrees,
• decreases to 105 degrees at 3 months, and is 71 degrees at birth and 68
• degrees in adulthood. The globe reaches its adult size by age 3 years, but the
• orbit is not of adult size until age 16 years.
• 5
• The extaocular muscles_are not OfneUrallcrest/origin; arise fromimyotonic
• Célls of the preoticregiony The extraocular muscles are of mesenchymal
• origin. The muscle cells are derived fromimesoderm) whereas the connective
• tissue components originate in neural crest. Extraocular muscles once were
• thought to develop in stages, first posteriorly near the orbital apex and then
• growing forward,6 but recent work suggests that muscle origin, belly, and
• insertion develop simultaneously. The muscles innervated by cranial nerve III
• are derived from the first pair of somites at approximately day 26. The lateral
• rectus muscle, innervated by cranial nerve VI, develops from the
• mesenchyme of the maxillomandibular area at about day 27. The
• superior oblique muscle, innervated by cranial nerve IV, is derived from the

second pair of somites at day 29.

NASOLACRIMAL SYSTEM

• The main lacrimal gland has long been thought to develop from epithelial
• buds that arise from the temporal portion of the conjunctiva of the superior
• fornix. The lacrimal gland continues to develop after birth and is not fully
• developed until age 3 or 4 years.
• The nasolacrimal drainage system develops from a cord of surface
• ectodermal cells that becomes buried below the maxillary mesenchyme
• Eyelids develop from surface ectoderm and mesenchyme as two skin folds
• (superior and inferior); the folds grow towards each other , and fuse at
• approximately 70 weeks of gestation (embryo size 45mm). The upper fold is
• from the frontonasal process, and the lower fold is from the maxillary
• process. The eyelid margins meet and fuse during the third month of
• development and remain fused until the lid structures have developed. Two
• layers of epithelium cover the anterior surface, and one layer lines the inner
• surface. The epithelial layers of the skin and conjunctiva, the hair follicles and
• cilia, and the meibomian glands, Zeis glands, and glands of Moll all develop
• from surface ectoderm; the tarsal plates, the orbicularis, the levator, and the
• tarsal muscle of Muller develop from mesenchyme. The fusion of the eyelids
• isolates the developing eye from the amniotic fluid and “probably prevents
• the cornea and conjunctiva from keratinizing.
• Between the 5” and 6" month of gestation the eyelids open.
• Faulty fusion of the folds ( facial processes), results in an eyelid coloboma.
• The upper eyelid is more commonly affected.
• Lens
• Induction occurs between the developing optic cup and the developing lens,
• apparently through a reciprocal relationship. As the surface ectoderm comes
• in contact with the optic vesicle, the invagination of the optic cup begins
• (approximately day 27), and the surface ectoderm adjacent to the vesicle
• begins to thicken, forming the lens plate (lens placode). If the area of
• contact between the optic vesicle and surface ectoderm is less than normal,
• a perfectly formed but microphthalmic eye will result. The center of the
• outer surface of the lens plate invaginates rapidly, forming a lens pit. As
• invagination continues, the lens vesicle is formed, which then separates from
• the surface ectoderm at approximately day 33. The lens vesicle is a hollow
• sphere composed of a single layer of cells surrounded by a thin basal lamina;
• with
• the addition of more material, the basal lamina will become the lens capsule.
• Once the lens vesicle is formed, the posterior epithelial cells adjacent to the
• future vitreous cavity elongate to fill in the lumen within the lens vesicle
• Mitosis, cell elongation, and lens fiber formation continue throughout
• development and throughout life. The orientation of the lens is influenced by
• the developing vitreous. The lens is initially spheric in shape but becomes

more ellipsoid with additional fibers

Hyaloid Arterial System

• Hyaloid artery produces a highly branching network that fills the vitreous
• cavity and
• forms the posterior vascular tunic of the lens (posterior tunica vasculosa
• lentis)
• The hyaloid vasculature reaches its peak development during the third
• month1 and begins to atrophy during the fourth month, at the same time

that the retinal vasculature is developing

BLOOD VESSEL PERMEABILITY AND BARRIERS

• The blood- retinal and blood- aqueous barriers are recognizable early in
• development in the tight junctions. formed in the RPE and the capillaries of

the ciliary body and iris