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Dr.LhachaWangdi,
1st
year resident (Ophthalmology)
UMSB,JDWNRH, 2014
Objectives
1. To understand the concept of origin and
developmental processes of human eye
2. To know the pathogenesis of congenital
anomalies of eye that may occur as a result of
defective embryogenesis
Presentation lay out
First session –
1. Development of primordial structures- general
embryology
2. Embryogenesis of anterior segment of eye
3. Congenital anomalies
Second session-
1. Embryogenesis of posterior segment of eye
2. Congenital anomalies
Introduction
The eyeball and its related structures are derived from
following primordia ;
1. Optic vesicle
2. lens placode
3. Mesoderm surrounding the optic vesicles
Derived from germ layers
 Ectoderm
 Mesoderm
 Endoderm
Embryology and regularity factors
 In embryology various endogenic regulatory factors controls
cellular differentiation, proliferation, cell migration and inductive
interaction for the specific organ development.
 Three groups of regularity factors are identified
1.Growth factors
2.Homeobox genes/ master
genes
3.Neural crest
cells
fibroblast
growth
factors(FGF)
transforming
growth factors
Bs
insulin
like growth
factors (IGF-I)
control subordinate genes
in regulation of patterns
of anatomical
development(morphogen
esis) eg. PAX6-marks the
location of lens, HOX
( HOX8.1 –corneal
epethelium,HOX7.1-
ciliarybody)
Transient
population of
pluripotent cells,
originated from
neuroectoderm
which latter
transforms into
mesenchymal cell
General Embryology
1. To understand the formation of germ layers
2. To know about the origin and formation of
ocular primordia
General embryology
 After fertilization of ovum it undergoes series of
cellular division/cleavage(1st
cell division-meiosos
followed by mitotic division)
 Forms morula ( 16 cell) stage by 4th
day
 Blastocyst (single cavity cell mass without zona
pellucida) by 5th
day
 Implantation of blastocyst occurs by 6th
day after
fertilazation
EARLY EMBRYONIC
STAGES
24 hours Day 2
Blastocyst-5th
day-ready for
implantation
Morula-4th
day
meiosis mitosis
1st
week embryology
Implantation of
Blastocyst by 6th
day
Fertilization –occurs 24
hours after ovulation at the
ampula of fallopian tube
Bilaminar embryonic disc-8th
day
 Formation of double layer cell from
embryoblast( Inner cell mass)
 With the formation of blastocyst , cells are
divided into inner cell mass call embryoblast
and out cell mass the tropoblast
 By 8th
day inner cell mass (embryoblast) is
divided into two layer ; epiblast and
hypoblast- the Bilaminar disc
bilaminar disc- 8th
day
HYPOBLAST
GASTRULATION-early 3rd
week
 Process of formation of three germinal
layers
 Begins with invagination of epiblastic cells
to form primitive streak by 16th
day
 Primitive streak is a central narrow groove
on the surface of epiblast formed by the
invagination of epiblastic cells
 Cells from epiblast starts migrating towards
the primitive streak
GASTRULATION-beginning 3rd
week
Primitive streak
GASTRULATION-early 3rd
week...
 Cells of primitive streak invaginates the
hypoblast and forms endoderm,
 Cells between epiblast and endoderm forms
mesoderm
 Cell remaining in epiblast becomes ectoderm
Gastruation-eaqrly 3rd
week
Bilaminar embryonic disc with
Migrating epiblastic cells
Gartrula with three germ
layers
Trilaminar disc- germ layer and ocular derivatives
NSR,RPE, pigmented ciliary
epithelium,nonpigmented
ciliary epithelium,pigmented
iris epithelium,smooth muscle
of iris,optic
nerve,vitreous,corneal stroma
and
endothelium,sclera,trabecular
meshwork,ciliary
muscle,melanocytes,meningeal
sheath,ciliary
ganglion,connective tissue of
orbit,lens,lacrimal gland and
drainage system,conjunctival
epithelium,connective tissue of
orbit, muscle layer and
connective tissue sheaths of all
ocular and blood vessels,
cartilage, choroidal
stroma,schwann cells
Fibers of extraocular muscle,
endothelial lining of all orbit and
ocular blood vessels, temporal
portion of sclera, vitreous
Neuraltion and neural tube formation-22th day
 Neural tube is an important primitive structure
from which ocular primordia-the optic vesicle, the
progenitor mesenchymal cell and neural tissue
develops
 Begins by proliferation of the surface ectodermal
cells to forms neural crest cells
 The crest cell moves medially to form neural
groove. Elevation of two side of neuroectoderm
forms neural fold and ultimately it fuses to become
neural tube
Neuraltion and neural tube
formation-22th day Neural
crest cell
Gartrula Neural grove
Neuraltion and neural tube formation-22th
day
1.Neural
plate
2.Neural
grove
3.Neural
tube Neural crest cell-
proginater cells for
mesenchymal cells
Surface
ectoderm
Formation of eye primordia-
3rd
week
 Primitive eye starts in 3rd
week of gestation when
anterior portion of neural tube is folding
 As the neural tube is folding 3 dilatation appears
at the anterior portion of neural tube-forebrain,
midbrain and hindbrain
 Primitive eye originates as Optic pit on either
side of midline in venterolateral region of
primitive forebrain
eye primordia-3rd
week
The optic pit/ocular
primordia
forebrain
Formation of optic and lens
vesicle Begins with the proliferation of
neuroectodermal cell of neural tube of
forebrain.
 Neural tube of forebrain grows laterally and
forms 2 globular structure at either side called-
primary optic vesicle
 With the formation of optic vesicle it induce
surface ectodermal cells to proliferate
 Surface ectoderm in contact with Optic vesicle
becomes lens plate/placode.
Ocular primordia
Cross section of neural
tube
ectoderm
mesoderm
endoderm
Lateral outgrowth of
neuroectoderm forms optic
vesicle
Neural tube
Lens plate
By end of 3rd
week gestation
 Three primordial structure are
formed:
1. Lens placode
2. Optic vesicle
3. Mesoderm surrounding
the optic vesicles
Concept of congenital anomalies
 Developmental anomalies Occurs due to
disturbance in embryonic events by various factors
in 1st
-3rd
months of pregnancy, ocular structures are
most at risk in the period of organogenesis from 18
– 60 days
1. Intrinsic factors 2.extrinsic factors(teratogen)
Altered, defective or imperfective
genes
Impaired cellular
induction/proliferation
Defective cell migration
Inadequate differentiation & cell
death
Infection (Rubella, syphilis,
cytomegalovirus, herpes simplex
virus
radiation
Maternal diseases(eg.Diabetes)
Drugs/toxins-
alcohol,thalidomide,antiseizure,retino
ic acid ets
Anterior segments-development
Development of eye structure are mostly
induced with the formation of optic
vesicle and lens placode .
Formation of lens
 Derived from surface
ectoderm
 With the formation of optic
vesicle the surface ectoderm
in contact with optic vesicle
thicken and forms lens
plate/lens placode-27th
day
 Eventually the lens plate
invaginates and separates
from surface ectoderm and
forms lens vesicle -33rd
day
Lens vesicle
 Lens vesicle has anterior wall with cuboidal
epithelial cell and posterior columnar epithelial
cells
Synthesize type 1v collagen
& gylcosaminoglycans to
form lens capsule,
maintains homeostatic
fuction of cell and serves as
progenitors for 2ndary
lens
fibers
Forms primary lens fiber-
embryonic nucleus
 Cells of posterior wall lengthens
and form elongated fiber that
projects into the lumen and
specific lens protein(crystalline)
are synthesized
 Posterior cell contributes for
most of the growth of lens for
first 2 month- embryonic
nucleus.
Posterior
epithelial cell
Primary lens fiber-
embryonic nucleus
 From 2nd
month the anterior progenitor
cells proliferates and produce 2ndary
lens
fibers also called fetal nucleus
 In 3rd
month inner most fibere mature
with increase in cytoplasmic fibrillar
materials and the cell nuclei and
organelles decreases
 Secondary fibers are displaced inward
between the capsule and embryonic
nucleus and meets on vertical planes to
form Y shape suture anteriorly and
inverted Y posteriorly
Lens
 At birth it weighs 90 mg (adult-255mg) with
thickness of 3.5mm ( adult-5mm)
 Lens fiber are formed throughout the human life
developing into different layers of lens fibers
Lens anomalies
 !
1.Congenital aphakia-absence of lens at birth
primary aphakia Secondary aphakia(more common)
Occurs due to failure of
surface ectoderm to
proliferate
Occurs due to spontaneous
absorption of developing lens
Associated with Alports syndrome-
X-linked disease characterized by
defective genes for production of
type 1V collagen
Lens anomalies
 Most are Idiopathic
 Herediatery-AD(most common),AR,X linked
 Genetic and metabolic disorders-Down
syndrome, marfans syndrome,galactosaemia
etc.
 Maternal infection and toxicity- rubella,
CMV,varicella,radiation etc
4.Congenital cataract-etiology
3.Lens coloboma-
flattening/notching of lens due to
absence of zonular fibers, associated with
defect in iris, optic nerve/ retina as a result
of abnormal closure of embryonic fissure
Development of cornea
 Development of cornea is
induced by lens and optic
vesicle formation
 With the separation lens vesicle
the surface ectodermal cell
proliferates to form epithelium
of cornea
 Basal lamina of epithelium cells
secrets collegen fibers and
gycosaminoglycans to form
primary stroma
Corneal
epithelium
Lens vesicle
Surface
ectoderm
Corneal embryogenesis-5th
week
 By early 5th
week gestation there
are 3 waves of mesenchymal
cells migrating towards the
corneal epithelium.
 1st
mesenchymal wave forms the
corneal endothelium.
 Desment’s membrane is derived
from the basal lamina of
endothelium
Ctn…
 3rd
mesenchymal wave
migrates between epithelium
and endothelium and forms
keratocytes
 The keratocytes synthesis type
1 collagen fibers and
proteoglycans which are
organized as lamellae to form
stroma of cornea
Corneal derivatives
 Diameter at birth –( 9.5-10.5)mm reaches adult
size 12 mm by 2 years
Derived from surface
ectoderm
Derived from
mesenchyme(neural
crest cell)
Derived from
mesenchyme(neural
crest cell)
Developmental anomalies-cornea
 Due to fetal arrest of corneal growth in 5th
month or
related to the overgrowth of anterior tips of optic cup
which leaves less space for cornea to develop
 Inherits as autosomal dominant/recessive trait
 Due to failure of optic cup to grow leaving large space
for cornea to fill
 Associated with abnormal collagen production-
Marfan syndrome
 Inherits as X-linked recessive pattern
1.Microcornea:
Corneal diameter is less than 9mm in
newborn or less than 10mm in adult
2.Megalocornea
Corneal diameter more tha 12mm at birth or more
than 13mm after 2 years
 Disorder of 2nd
wave mesenchymal migration
 90% bilateral
 Sporadic but both autosomal dominant and
recessive inheritance pattern are reported
 Endothelial dystrophy-Primary dysfunction of 1st
mesenchymal wave/corneal endothelial cell
degeneration. Autosomal recessive>dominant.
 Stromal dystrophy –dysfunction of corneal stroma
causing corneal opacity.
3.Sclerocornea-
Sclera like clouding of cornea with ill-defined limbus.
Difficult to differentiate cornea and sclera
4.Corneal Dystrophy
Diffuse,ill defined flaky/featheary/blue-gray ground
glass opacification of cornea. Cornea is clearer
peripherally
 Corneal thinning and bulging due stromal and epithelium
thinning, fragmentation of Bowman’s layer and folds or break
in Descement’s membrane
 Etiology unknown, usually multifactorial associated with Down
syndrome, mental retardation and atopic diseases
5.keratoconus-
Condition in which central cornea assume a conical shape
THANK YOU
End of 1st
session
References
1.American Academy of Ophthalmology
(BCSC-section 2, 2012-2013)
2.Langmans medical embryology
3.Oxford Text Book of ophthalmology
(volume 11-section2.16.1-Embryology of eye
and orbit by Garry N.Shuttleworth)
4.Internet resources
Embryology of eye
Session 11
Recap
General embryology
 Development of embryoblast from inner cell mass of blastocyst which
differentiate into bilaminar disc (epiblast and hypoblast)
 Formation of three germ layers and neuralation
 Ocular origin and primordia
 Derivatives of ocular structure (ectoderm and mesoderm)
 Formation of optic vesicle, lens placode/plate
 Embryogenesis of lens and cornea
 Developmental anomalies of cornea and lens
Session 11-Outline
 Origin and developmental processes of
anterior and posterior segment of eye
 Developmental anomalies
Anterior chamber and angle formation
 By beginning of 3rd
week there are three successive
in growth of mezenchymal cell surrounding the
optic cup
 1st
wave of mezenchye forms corneal endothelium,
2nd
waves forms pupillary membrane and 3rd
wave
forms the keratocytes of cornea
 Anterior chamber is first recognized as split like
space between developing corneal endothelium and
iris epithelium as a result of selective mezenchymal
cell atrophy/cleavage
Anterior chamber and angle formation
1st
Mesenchymal
wave form corneal
endothelium
2nd
wave forms
pupillary membrane
3rd
wave forms
keratocytes of
cornea
Primitive
anterior
chamber-slitlike
space
 By 15th
week of gestation corneal
endothelial cells extend into the angle
recess and meets with iris epithelium
 By 3rd
month angle recess deepens and
forms iridocorneal angle
 In 7th
week – the angle of the anterior
chamber is occupied by the
mesenchymal cells of neural crest origin-
forms trabecular meshwork
 Schlemm canal develops from small
plexus of venous canaliculi of
endodermal origin and forms
uveoscleral outflow/tract.
Trabecular meshwork
 The anterior chamber angle continuous to recede until 6-12
month after birth when it become adult type appearance.
 Anterior chamber depth is 2.3-2.7 mm at birth (adult-3mm)
 In the final week gestation the
trabecular meshwork undergoes
fenestration and communicates with
anterior chamber
 Congenital glaucoma may occur as a
result of defect in terminal
differentiation of trabecular tissue
leading to excessive formation of
meshwork collegen preventing
formation of iridocorneal angle
Ciliary body and iris- outline
 By 3rd
week gestation there is
extension of 2 layers of
neuroectoderm from the edge of optic
cup
 Its has outer pigmented
epithelium(PE) and inner non
pigmented epithelium(NPE)
 Distal part of advancing
neuroectoderm becomes an iris
 Proximal part of neuroectoderm
extension becomes the ciliary body
Ciliary body-ctn..
 Cellular proliferation of proximal 2 layers of
neuroectoderm forms longitudinal indentation
of outer pigmented epithelium
 By 12 weeks Inner non pigmented layer forms
radial fold(75) and become ciliary processes
 At 10 week mezenchymal cells get condensed
at its anterior surface to form the stroma of
ciliary body
 At 12 weeks there is Myofillament proliferation
of mezenchyme and forms smooth muscles of
ciliary body by 5th
month
 Ciliary muscle continues to develop for at least
1year after birth.
Ciliary body
 By 4th
month ciliary body is
functional and secrets
aqueous humour which fills
up anterior and posterior
chamber
 Ciliary epithelium synthesis
collagen fibers which
becomes suspensory
ligament/zonules of lens
Development of iris-3rd
month
 Developed from 2 layers;
1. Mesenchyme-anterior stroma
2.Neuroectoderm of optic cup–
- iris pigment epithelium
-sphinchte and dilater muscles
 Iris begins to develop by condensation
of 2nd
wave mezenchymal to form
Pupillary membrane
Formation of pupillary membrane-early 3rd
month Pupillary membrane is formed by Condensation of 2nd
wave
mesenchymal cell forms pupilary membrane
Lens
vesicle
Optic cup
Condensation of
mesenchymal cells
cornea
Pupillarey membrane
Iris epithelium-end of 3rd
month
 2 layers of neuroectoderm from
the edge of optic cup extend to
the posterior surface of pupillary
membrane.
 Three structures(PE,NPE and
pupillary membrane) ultimately
fuses to become an iris
Pupillary
membrane
Iris- 3rd month
 At 3rd
month Cells of anterior epithelium
layer differentiates into myofobrills and
forms sphincter and dilator muscles of an
iris
 Pupillary Membrane(PM)-cells of PM
differentiates into fibroblast like cell and
secrets collegen fibrills & extracelluler
matrix which is incorporated with PE to
form the anterior stroma of an iris

 pigmentation of posterior epithelial
cell occurs begins at the pupillary
margin at midterm , by 7th
month
iris is fully pigmented
Iris and pupil-8th
month gestation
 Pupillary membrane begins
to degenerate at about 8th
months of gestation
 Opening in the central part
of iris forms the pupil
 Iris stroma and dilator
muscle is still immature at
birth-pupil appears miotic
at birth
Iris anomalies
 Can be Associated with syndromic presentation like trisomy 13,
klinefelter,turner, CHARGE association(ocular coloboma,heart defects, choanal
atresia, mental retardation, genitourinary and ear anomalies)
1.Hypoplasia/absence of an iris
Inadequate inductive interactive between optic cup, surface
ectoderm and neural crest cell due to Defect in PAX6 genes
Occurs as sporadic or autosomal dominant
2.Persistant pupillary membrane
Most common congenital iris anomalies
Failure to atrophy pupillary membrane
3.Iris Coloboma
Failure of embryonic fissure to close in 5th
week gestation
Pupil appears like inverted tear drop usually at the
inferonasal quadrant
Can be associated wit coloboma of choroid, retina, ciliary
body and optic nerve
Iris anomalies…
7.Conginatal mydriasis
Mlafoamation of iris sphincter muscle
4.polycoria -Accessory iris opening
Associated with Axenfeld-Reiger Syndrome ( autosomal
dominant disorder) due to mutation of PAX and FOXC1
gene
Present with ,malformation of face, teeth, skeletal
system
5.Corectopia-Displacement of pupil
Associated with sector iris hypoplasia or colobomatous
lession or lens subluxation(ectopia lentis et pupillae)
6.microcoria-congenital miosis
Occurs due to malformation of dilator pupillae muscle
Can be associated with microcornea,lens subluxation,
iris atrophy and glaucoma
Posterior chamber
 Develops as a slit in the mesenchyme
posterior to the developing iris and anterior
to the developing lens
 Anterior and posterior communicates when
the pupillary membrane disappears and the
pupil is formed
 Aqueous humor fills these two chamber
Embryogenesis-Posterior
segment Retina
 Optic nerve
 Vitreous
 Choroid
 Sclera
 Vascular system
Retina-originates from ectoderm
 Neurosensory retina-
originates from the inner layer
of neuroectodermal cell of
optic cup
 Retinal pigment epithelium-
Originates from the outer
neuroectodermal cell of an
optic cup
Neurosensory layer-1st
month(3-4 rows of
cells)  Anterior 1/5th
– forms the posterior
surface of developing ciliary and iris
 Posterior 4/5th
forms the primordial
sensory retina
 Mitotic cellular differentiation at
primordial retina forms two 2 distinct
layers by 7th
week
 Outer 2/3rd
–primitive nuclear zone has
rows of nucleated cells which will
forms neural cells
 Inner 1/3rd
- marginal zone has cells
devoid of nucleus which will form
nerve fiber layers)
Neurosensory(NSR) retina
 NSR begins to develop from outer primitive
nuclear zone(PNZ)
 Cellular proliferation of PNZ forms nuclear
and glial cells which are organized as 2
distinctive zones
1. Outer neuroblastic layer(forms
photoreceptors)
2. Inner neuroblastic layer(Ganglion cell
layers)
3. Two neuroblastic layer are seperated by
transient nerve fiber layer of Chievitz which
become inner plexiform layer by 9th
week
gestation
Primitive nerve fiber
NSR formation…ctn…
 Differentiation of outer neuroblastic layers
occurs(ONL)by 5th
week and form
photoreceptors(rods and cones)
 Cellular differentiation of ONL also forms bipolar,
amacrine, horizontal cells and form inner nucleated
layers of retina
 Ganglion cell appears in inner neuroblastic layers and
form ganglion cell layer
 Axons from ganglion cell develops at 6th
week and
form primitive nerve fiber layers
Retina-cells and synapses formation
Optic cup
Primitive nuclear zone
Inner marginal
zone forms nerve
fiber layers
Inner
neuroblastic
layer
Outer
neuroblastic
layer
Primitive neurosensory
retina
 Cellular proliferation and melanogenesis of outer wall of
optic cup begins by 6th
week and forms retinal pigment
epithelium
 By 15 week gestation all cells types , synapses and
intercellular junction of neurosensory retina are
formed
 Fovea is formed by thinning of ganglion and inner
nucleated layer by 24 weeks
Retina by 5th
week  Retinal pigment epithelium
developed from outer layer
of an optic cup
 Outer segment-
photoreceptors
 Outer nucleated layers
retina
 Outer plexiform layers
 Inner nucleated layers
 Inner plexifor layers
 Ganglion layer
 Nerve fiber layer
Derived
from outer
neuroblastic
layer
Derived from
inner
neuroblastic
layer
Optic nerve
 Develops from optic
stalk(connection between
optic vesicle and forebrain)
 Initially optic stalk has two
layers
1. Inner neuroectodermal cells
layer
2. Outer undifferentiated
neural crest cells layer
Optic nerve formation
Late in 6th
week, cells of inner layer of optic
nerve degenerates and become vacuolated
Nerve fibers (axons) from the ganglion cells
migrates through the vacuolated space of
optic stalk
By 33 weeks it establishes an adult type optic
nerve of 1.1 million of axons
Few cells of inner layer differentiated into
glial cell which forms lamina cribosa by 8th
week.
 Outer neural crest cells differentiates into (1)pia, (2)arachnoid
and (3)dura matter which form optic nerve sheath by 4th
month
Optic nerve
Ganglion cell layer
Axons from
ganglion cells
Optic disc
Optic nerve
Optic anomalies
1.Morning glory disc anomaly
Appears as funnel shaped excavation of the
posterior fundus that incorporates the disc.
Occurs due to abnormal closure of embryonic
fissure
2.Coloboma of optic nerve.
May occurs as a part of chorioretinal
coloboma or solitary abnormality
Due to failure of embryonic fissure to close
Can be associated with systemic
abnormalities-CHARGE association
3.
Formation of vitreous
 Develops between lens and optic cup
 Mostly derived from mesoderm with minimal
contribution from ectoderm
 Formation of vitreous occurs in three stages ;
❶ Primary vitreous
❷Secondary vitreous
❸Tertiary vitreous
Primary vitreous-1st
month of gestation
 Network of delicate cytoplasmic
process which occupy the space
between lens vesicle and inner
layer of optic cup
 It is composed of fibrils
(ectoderm) and mesenchymal
cells(mesoderm) which
constitutes primary vitreous
 Supplied by hyaloid vessels and
its branches
Secondary vitreous- 2nd
month of gestation
 By 2nd
month the hyaloid system
regresses and primary vitreous cell
differentiates into hyalocytes which
synthesis type 11 collagen and
hyaluronic acid which constitutes
secondary vitreous
 2nd
vitreous is avascular gel like
substances occupying the space
between primary vitreous and retina
 By 5th
-6th
month primary vitreous and
Hyaloid vessels undergoes atrophy.
 Atrophied hyaloid vessels become
hyaloid cannal which remain
throughout the life as Cloquet canal
Primary vitreous
Tertiary vitreous-3rd
month
 It is Formation of zonular fiber between the ciliary
body and lens capsule
 Collagen fibrils synthesized by
ciliary epithelium becomes more
condensed and extends to the
lens equator and become zonular
fiber of lens which constitutes
the tertiary vitreous
Persistent hyperplastic primary
vitreous(PHPV)
 Presents as leukocoria-white pupillary reflex
 Its occurs due to failure of
primary vitreous and hyaloid
vessels to regress
 None hereditary and not
associated with systemic defects.
Choroid
 Vascular endothelium and the haemopoietic cells of
choroid are derived from endoderm
 Choroidal stroma ( vascular pericytes, smooth muscles,
melanocytes and collagenous components) of choroid
are derived from ectoderm.
 Choroidal development is
associated with the
condensation of neural
crest cells around the optic
cup
Choroid..cntn
 Differentiation of neural crest
cells form choroidal stroma by
the end of 3rd
month gestation
 Endothelium line blood vessels appears in
the choroid stroma and forms
choriocapillary
 By 4the week Choriocapillary begins to
differentiate and by 2nd
month it anastomosis
with short ciliary artery
 By 8th
month final arterial circulation of
choroid is established after anastomosis with
vessels of ciliary body and iris
Sclera
 Sclera is mostly ectodermal (neural crest) in origin,
however posterior region are mesoderm in origin
 Sclera begins to develop by
condensation of mesenchymal cells
around the anterior rim of optic cup
 Mesenchymal cells proliferates and
deposits glycosaminoglycans, collagen
and elastin fibrils and forms stroma of
sclera
 By 5th
month sclera is relatively well
formed
Vascular system of eye- overview
 Arterial wall has three layers;
1. Tunica adventitia(connective tissue)
2. Tunica media(smooth muscle layer)
3. Tunica intima( endothelium)
 Tunica adventitia and tunica media of ocular vessels are
derived from neural crest cells(ectoderm)
 Tunica intima is derived from endoderm
Primitive orbital vessels
 During early embryonic life
untill 8th
month, the
developing ocular structure is
nourished by three transient
vessels originating from
internal carotid artery;
A.Ventral ophthalmic artery
B. Dorsal ophthalmic artery
F. Stapedial artery
 Ventral artery later atrophy and only a portion remain as long
posterior nasal ciliary artery
 Dorsal ophthalmic artery become definitive ophthalmic artery
 Stapedial artery becomes Middle meningeal artery
Internal carotid artery
Primitive ocular vessels
Embryonic intraocular vasculature system has
two components;
1.Anterior system- supplies anterior segment
 formed in iris and pupillary membrane
 formed by the branches of ophthalmil artery- anterior
ciliary artery and posterior long ciliary artery
2.Posterior system- supplies posterior segment
 formed within the vitreous
 formed by hyaloid vascular system
Anterior artery system
 Anterior artery system is formed by
posterior long,short ciliary artery and
anterior ciliary artery which are the
branches of dorsal opthalmic artery
 Anastomosis of ciliary arteries forms
major arterial circle at the root of iris
 Vascular twigs from major arterial cicle
and annular vessels forms the pupialiary
arcade
 With the disappearance of pupillary
membrane pupilliary arcade remain
peripherally as minor artery circle which
supply iris
Posterior
ciliary artery
Anterior
ciliary artery
Posterior arterial system
Hyaloid artery nourishes the
developing eye globe until
the 8th
month of gestation
Hyaloid artery is the branch
of primitive dorsal
ophthalmic artery
Later the Hyaloid artery
regresses and become
central retinal artery
Atrophied
ventral artery
Dorsal artery
Hyaloid system….
 As the optic vesicle develops there
is incomplete folds in its inferior
portion of cup and stalk called
embryonic fissure
 Embryonic fissure allows hyaloid
system to be incorporated within
the eye.
 In 3rd
week Hyaloid artery enters
the embryonic fissure of optic
stalk.
 With the fusion of fissure the
hyaloid system are enclosed
within the eye
Clinical application
 Failure to close embryonic fissure causes
colobomatous deformaties of an iris, choroid,
retina and optic nerve
Hyaloid system
 Branches of the hyaloid artery supplies developing lens,
vitreous, optic nerve
 Anastomosis of branches of hyaloid artery forms 3
arterial arcades calledTunica vasculosa Lentis
1.Anterior vascular capsule
2.Capsulopupialary portion
3.Posterior vascular capsule
Valsa hyaloida propria(small
capillary branches)
Hyaloid artery
Retinal circulation
 By 4th
month the hyaloid artery bud of to from
central retinal artery
 Hyaloid artery system atrophy and regresses in
3rd
trimester
 Retinal artery vascularizes the retinal
 Nasal retina completes vascularization prior to
temporal retina
 By 8th
month all retinal part are vascularized
except for portion of peripherals temporal retina
which completes 3 months after birth
Retinal circulation
 Atrophied hyaloid system
 Retinal vessels buds from
hyaloid artery and
vascularizes retina
 Vascularization reaches
nasal ora serrata by 8th
month and temporal ora
serrata by 2 month after
birth
Retinopathy of prematurity
 Ischemia triggers abnormal vessel formation called
neovascularization-retinopathy of prematurity
 Premature baby has incomplete
vascularization of retina
 Hyperoxia(supplementary
oxygenation) causes
vasoconstriction
 Vasoconstriction causes
ischemia in the incompletely
developed retinal periphery
Summary-Derivatives
Ocular structures Derivatives
Cornea
Ectoderm
Ectoderm
Ectoderm and neural crest cells
Vitreous
EctodermCiliary body
Neural crest cell(ectoderm)Trabecular meshwork
Lens
Iris
Choroid
ectodermRetina
Ectoderm and mesoderm
ectodermOptic nerve
Ectoderm & mesodermSclera
Ectoderm
Mesoderm & ectodermOcular vessels
Human eye at birth and after
birth Eye grows rapidly during first 2 years of life
until puberty
 Most young children are hyperopic of 3.0 D
because of less axial length of eye( at birth
17mm, adult 24mm)
 Corneal diameter is 9.5-10.5 at birth and 12
mm in adults
 Radius of corneal curvature is 6.6-7.4 mm at
birth and 7.4-8.4 in adults
…………continue
Newborn has miotic pupil because dilator pipillae
muscle is not well form at birth
Visual development
Pupillary light reflux-present after 31 week of gestation
Blink reflex to light- several days after birth
6 weeks-maintain eye contact and react with facial
expression
2-3months –preferential to bright objects
References
1. American Academy of Ophthalmology
(BCSC-section 2-fundamentas and principles
of ophthalmology
BCSC-section6-pediatric ophthalmology)
2.Langmans medical embryology
3.Oxford Text Book of ophthalmology
4.Internet resources

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Embryology of human eye

  • 2. Objectives 1. To understand the concept of origin and developmental processes of human eye 2. To know the pathogenesis of congenital anomalies of eye that may occur as a result of defective embryogenesis
  • 3. Presentation lay out First session – 1. Development of primordial structures- general embryology 2. Embryogenesis of anterior segment of eye 3. Congenital anomalies Second session- 1. Embryogenesis of posterior segment of eye 2. Congenital anomalies
  • 4. Introduction The eyeball and its related structures are derived from following primordia ; 1. Optic vesicle 2. lens placode 3. Mesoderm surrounding the optic vesicles Derived from germ layers  Ectoderm  Mesoderm  Endoderm
  • 5. Embryology and regularity factors  In embryology various endogenic regulatory factors controls cellular differentiation, proliferation, cell migration and inductive interaction for the specific organ development.  Three groups of regularity factors are identified 1.Growth factors 2.Homeobox genes/ master genes 3.Neural crest cells fibroblast growth factors(FGF) transforming growth factors Bs insulin like growth factors (IGF-I) control subordinate genes in regulation of patterns of anatomical development(morphogen esis) eg. PAX6-marks the location of lens, HOX ( HOX8.1 –corneal epethelium,HOX7.1- ciliarybody) Transient population of pluripotent cells, originated from neuroectoderm which latter transforms into mesenchymal cell
  • 6. General Embryology 1. To understand the formation of germ layers 2. To know about the origin and formation of ocular primordia
  • 7. General embryology  After fertilization of ovum it undergoes series of cellular division/cleavage(1st cell division-meiosos followed by mitotic division)  Forms morula ( 16 cell) stage by 4th day  Blastocyst (single cavity cell mass without zona pellucida) by 5th day  Implantation of blastocyst occurs by 6th day after fertilazation
  • 8. EARLY EMBRYONIC STAGES 24 hours Day 2 Blastocyst-5th day-ready for implantation Morula-4th day meiosis mitosis
  • 9. 1st week embryology Implantation of Blastocyst by 6th day Fertilization –occurs 24 hours after ovulation at the ampula of fallopian tube
  • 10. Bilaminar embryonic disc-8th day  Formation of double layer cell from embryoblast( Inner cell mass)  With the formation of blastocyst , cells are divided into inner cell mass call embryoblast and out cell mass the tropoblast  By 8th day inner cell mass (embryoblast) is divided into two layer ; epiblast and hypoblast- the Bilaminar disc
  • 12. GASTRULATION-early 3rd week  Process of formation of three germinal layers  Begins with invagination of epiblastic cells to form primitive streak by 16th day  Primitive streak is a central narrow groove on the surface of epiblast formed by the invagination of epiblastic cells  Cells from epiblast starts migrating towards the primitive streak
  • 14. GASTRULATION-early 3rd week...  Cells of primitive streak invaginates the hypoblast and forms endoderm,  Cells between epiblast and endoderm forms mesoderm  Cell remaining in epiblast becomes ectoderm
  • 15. Gastruation-eaqrly 3rd week Bilaminar embryonic disc with Migrating epiblastic cells Gartrula with three germ layers
  • 16. Trilaminar disc- germ layer and ocular derivatives NSR,RPE, pigmented ciliary epithelium,nonpigmented ciliary epithelium,pigmented iris epithelium,smooth muscle of iris,optic nerve,vitreous,corneal stroma and endothelium,sclera,trabecular meshwork,ciliary muscle,melanocytes,meningeal sheath,ciliary ganglion,connective tissue of orbit,lens,lacrimal gland and drainage system,conjunctival epithelium,connective tissue of orbit, muscle layer and connective tissue sheaths of all ocular and blood vessels, cartilage, choroidal stroma,schwann cells Fibers of extraocular muscle, endothelial lining of all orbit and ocular blood vessels, temporal portion of sclera, vitreous
  • 17. Neuraltion and neural tube formation-22th day  Neural tube is an important primitive structure from which ocular primordia-the optic vesicle, the progenitor mesenchymal cell and neural tissue develops  Begins by proliferation of the surface ectodermal cells to forms neural crest cells  The crest cell moves medially to form neural groove. Elevation of two side of neuroectoderm forms neural fold and ultimately it fuses to become neural tube
  • 18. Neuraltion and neural tube formation-22th day Neural crest cell Gartrula Neural grove
  • 19. Neuraltion and neural tube formation-22th day 1.Neural plate 2.Neural grove 3.Neural tube Neural crest cell- proginater cells for mesenchymal cells Surface ectoderm
  • 20. Formation of eye primordia- 3rd week  Primitive eye starts in 3rd week of gestation when anterior portion of neural tube is folding  As the neural tube is folding 3 dilatation appears at the anterior portion of neural tube-forebrain, midbrain and hindbrain  Primitive eye originates as Optic pit on either side of midline in venterolateral region of primitive forebrain
  • 21. eye primordia-3rd week The optic pit/ocular primordia forebrain
  • 22. Formation of optic and lens vesicle Begins with the proliferation of neuroectodermal cell of neural tube of forebrain.  Neural tube of forebrain grows laterally and forms 2 globular structure at either side called- primary optic vesicle  With the formation of optic vesicle it induce surface ectodermal cells to proliferate  Surface ectoderm in contact with Optic vesicle becomes lens plate/placode.
  • 23. Ocular primordia Cross section of neural tube ectoderm mesoderm endoderm Lateral outgrowth of neuroectoderm forms optic vesicle Neural tube Lens plate
  • 24. By end of 3rd week gestation  Three primordial structure are formed: 1. Lens placode 2. Optic vesicle 3. Mesoderm surrounding the optic vesicles
  • 25. Concept of congenital anomalies  Developmental anomalies Occurs due to disturbance in embryonic events by various factors in 1st -3rd months of pregnancy, ocular structures are most at risk in the period of organogenesis from 18 – 60 days 1. Intrinsic factors 2.extrinsic factors(teratogen) Altered, defective or imperfective genes Impaired cellular induction/proliferation Defective cell migration Inadequate differentiation & cell death Infection (Rubella, syphilis, cytomegalovirus, herpes simplex virus radiation Maternal diseases(eg.Diabetes) Drugs/toxins- alcohol,thalidomide,antiseizure,retino ic acid ets
  • 26. Anterior segments-development Development of eye structure are mostly induced with the formation of optic vesicle and lens placode .
  • 27. Formation of lens  Derived from surface ectoderm  With the formation of optic vesicle the surface ectoderm in contact with optic vesicle thicken and forms lens plate/lens placode-27th day  Eventually the lens plate invaginates and separates from surface ectoderm and forms lens vesicle -33rd day
  • 28. Lens vesicle  Lens vesicle has anterior wall with cuboidal epithelial cell and posterior columnar epithelial cells Synthesize type 1v collagen & gylcosaminoglycans to form lens capsule, maintains homeostatic fuction of cell and serves as progenitors for 2ndary lens fibers Forms primary lens fiber- embryonic nucleus
  • 29.  Cells of posterior wall lengthens and form elongated fiber that projects into the lumen and specific lens protein(crystalline) are synthesized  Posterior cell contributes for most of the growth of lens for first 2 month- embryonic nucleus. Posterior epithelial cell Primary lens fiber- embryonic nucleus
  • 30.  From 2nd month the anterior progenitor cells proliferates and produce 2ndary lens fibers also called fetal nucleus  In 3rd month inner most fibere mature with increase in cytoplasmic fibrillar materials and the cell nuclei and organelles decreases  Secondary fibers are displaced inward between the capsule and embryonic nucleus and meets on vertical planes to form Y shape suture anteriorly and inverted Y posteriorly
  • 31. Lens  At birth it weighs 90 mg (adult-255mg) with thickness of 3.5mm ( adult-5mm)  Lens fiber are formed throughout the human life developing into different layers of lens fibers
  • 32. Lens anomalies  ! 1.Congenital aphakia-absence of lens at birth primary aphakia Secondary aphakia(more common) Occurs due to failure of surface ectoderm to proliferate Occurs due to spontaneous absorption of developing lens Associated with Alports syndrome- X-linked disease characterized by defective genes for production of type 1V collagen
  • 33. Lens anomalies  Most are Idiopathic  Herediatery-AD(most common),AR,X linked  Genetic and metabolic disorders-Down syndrome, marfans syndrome,galactosaemia etc.  Maternal infection and toxicity- rubella, CMV,varicella,radiation etc 4.Congenital cataract-etiology 3.Lens coloboma- flattening/notching of lens due to absence of zonular fibers, associated with defect in iris, optic nerve/ retina as a result of abnormal closure of embryonic fissure
  • 34. Development of cornea  Development of cornea is induced by lens and optic vesicle formation  With the separation lens vesicle the surface ectodermal cell proliferates to form epithelium of cornea  Basal lamina of epithelium cells secrets collegen fibers and gycosaminoglycans to form primary stroma Corneal epithelium Lens vesicle Surface ectoderm
  • 35. Corneal embryogenesis-5th week  By early 5th week gestation there are 3 waves of mesenchymal cells migrating towards the corneal epithelium.  1st mesenchymal wave forms the corneal endothelium.  Desment’s membrane is derived from the basal lamina of endothelium
  • 36. Ctn…  3rd mesenchymal wave migrates between epithelium and endothelium and forms keratocytes  The keratocytes synthesis type 1 collagen fibers and proteoglycans which are organized as lamellae to form stroma of cornea
  • 37. Corneal derivatives  Diameter at birth –( 9.5-10.5)mm reaches adult size 12 mm by 2 years Derived from surface ectoderm Derived from mesenchyme(neural crest cell) Derived from mesenchyme(neural crest cell)
  • 38. Developmental anomalies-cornea  Due to fetal arrest of corneal growth in 5th month or related to the overgrowth of anterior tips of optic cup which leaves less space for cornea to develop  Inherits as autosomal dominant/recessive trait  Due to failure of optic cup to grow leaving large space for cornea to fill  Associated with abnormal collagen production- Marfan syndrome  Inherits as X-linked recessive pattern 1.Microcornea: Corneal diameter is less than 9mm in newborn or less than 10mm in adult 2.Megalocornea Corneal diameter more tha 12mm at birth or more than 13mm after 2 years
  • 39.  Disorder of 2nd wave mesenchymal migration  90% bilateral  Sporadic but both autosomal dominant and recessive inheritance pattern are reported  Endothelial dystrophy-Primary dysfunction of 1st mesenchymal wave/corneal endothelial cell degeneration. Autosomal recessive>dominant.  Stromal dystrophy –dysfunction of corneal stroma causing corneal opacity. 3.Sclerocornea- Sclera like clouding of cornea with ill-defined limbus. Difficult to differentiate cornea and sclera 4.Corneal Dystrophy Diffuse,ill defined flaky/featheary/blue-gray ground glass opacification of cornea. Cornea is clearer peripherally
  • 40.  Corneal thinning and bulging due stromal and epithelium thinning, fragmentation of Bowman’s layer and folds or break in Descement’s membrane  Etiology unknown, usually multifactorial associated with Down syndrome, mental retardation and atopic diseases 5.keratoconus- Condition in which central cornea assume a conical shape
  • 41. THANK YOU End of 1st session
  • 42. References 1.American Academy of Ophthalmology (BCSC-section 2, 2012-2013) 2.Langmans medical embryology 3.Oxford Text Book of ophthalmology (volume 11-section2.16.1-Embryology of eye and orbit by Garry N.Shuttleworth) 4.Internet resources
  • 44. Recap General embryology  Development of embryoblast from inner cell mass of blastocyst which differentiate into bilaminar disc (epiblast and hypoblast)  Formation of three germ layers and neuralation  Ocular origin and primordia  Derivatives of ocular structure (ectoderm and mesoderm)  Formation of optic vesicle, lens placode/plate  Embryogenesis of lens and cornea  Developmental anomalies of cornea and lens
  • 45. Session 11-Outline  Origin and developmental processes of anterior and posterior segment of eye  Developmental anomalies
  • 46. Anterior chamber and angle formation  By beginning of 3rd week there are three successive in growth of mezenchymal cell surrounding the optic cup  1st wave of mezenchye forms corneal endothelium, 2nd waves forms pupillary membrane and 3rd wave forms the keratocytes of cornea  Anterior chamber is first recognized as split like space between developing corneal endothelium and iris epithelium as a result of selective mezenchymal cell atrophy/cleavage
  • 47. Anterior chamber and angle formation 1st Mesenchymal wave form corneal endothelium 2nd wave forms pupillary membrane 3rd wave forms keratocytes of cornea Primitive anterior chamber-slitlike space
  • 48.  By 15th week of gestation corneal endothelial cells extend into the angle recess and meets with iris epithelium  By 3rd month angle recess deepens and forms iridocorneal angle  In 7th week – the angle of the anterior chamber is occupied by the mesenchymal cells of neural crest origin- forms trabecular meshwork  Schlemm canal develops from small plexus of venous canaliculi of endodermal origin and forms uveoscleral outflow/tract.
  • 49. Trabecular meshwork  The anterior chamber angle continuous to recede until 6-12 month after birth when it become adult type appearance.  Anterior chamber depth is 2.3-2.7 mm at birth (adult-3mm)  In the final week gestation the trabecular meshwork undergoes fenestration and communicates with anterior chamber  Congenital glaucoma may occur as a result of defect in terminal differentiation of trabecular tissue leading to excessive formation of meshwork collegen preventing formation of iridocorneal angle
  • 50. Ciliary body and iris- outline  By 3rd week gestation there is extension of 2 layers of neuroectoderm from the edge of optic cup  Its has outer pigmented epithelium(PE) and inner non pigmented epithelium(NPE)  Distal part of advancing neuroectoderm becomes an iris  Proximal part of neuroectoderm extension becomes the ciliary body
  • 51. Ciliary body-ctn..  Cellular proliferation of proximal 2 layers of neuroectoderm forms longitudinal indentation of outer pigmented epithelium  By 12 weeks Inner non pigmented layer forms radial fold(75) and become ciliary processes  At 10 week mezenchymal cells get condensed at its anterior surface to form the stroma of ciliary body  At 12 weeks there is Myofillament proliferation of mezenchyme and forms smooth muscles of ciliary body by 5th month  Ciliary muscle continues to develop for at least 1year after birth.
  • 52. Ciliary body  By 4th month ciliary body is functional and secrets aqueous humour which fills up anterior and posterior chamber  Ciliary epithelium synthesis collagen fibers which becomes suspensory ligament/zonules of lens
  • 53. Development of iris-3rd month  Developed from 2 layers; 1. Mesenchyme-anterior stroma 2.Neuroectoderm of optic cup– - iris pigment epithelium -sphinchte and dilater muscles  Iris begins to develop by condensation of 2nd wave mezenchymal to form Pupillary membrane
  • 54. Formation of pupillary membrane-early 3rd month Pupillary membrane is formed by Condensation of 2nd wave mesenchymal cell forms pupilary membrane Lens vesicle Optic cup Condensation of mesenchymal cells cornea Pupillarey membrane
  • 55. Iris epithelium-end of 3rd month  2 layers of neuroectoderm from the edge of optic cup extend to the posterior surface of pupillary membrane.  Three structures(PE,NPE and pupillary membrane) ultimately fuses to become an iris Pupillary membrane
  • 56. Iris- 3rd month  At 3rd month Cells of anterior epithelium layer differentiates into myofobrills and forms sphincter and dilator muscles of an iris  Pupillary Membrane(PM)-cells of PM differentiates into fibroblast like cell and secrets collegen fibrills & extracelluler matrix which is incorporated with PE to form the anterior stroma of an iris   pigmentation of posterior epithelial cell occurs begins at the pupillary margin at midterm , by 7th month iris is fully pigmented
  • 57. Iris and pupil-8th month gestation  Pupillary membrane begins to degenerate at about 8th months of gestation  Opening in the central part of iris forms the pupil  Iris stroma and dilator muscle is still immature at birth-pupil appears miotic at birth
  • 58. Iris anomalies  Can be Associated with syndromic presentation like trisomy 13, klinefelter,turner, CHARGE association(ocular coloboma,heart defects, choanal atresia, mental retardation, genitourinary and ear anomalies) 1.Hypoplasia/absence of an iris Inadequate inductive interactive between optic cup, surface ectoderm and neural crest cell due to Defect in PAX6 genes Occurs as sporadic or autosomal dominant 2.Persistant pupillary membrane Most common congenital iris anomalies Failure to atrophy pupillary membrane 3.Iris Coloboma Failure of embryonic fissure to close in 5th week gestation Pupil appears like inverted tear drop usually at the inferonasal quadrant Can be associated wit coloboma of choroid, retina, ciliary body and optic nerve
  • 59. Iris anomalies… 7.Conginatal mydriasis Mlafoamation of iris sphincter muscle 4.polycoria -Accessory iris opening Associated with Axenfeld-Reiger Syndrome ( autosomal dominant disorder) due to mutation of PAX and FOXC1 gene Present with ,malformation of face, teeth, skeletal system 5.Corectopia-Displacement of pupil Associated with sector iris hypoplasia or colobomatous lession or lens subluxation(ectopia lentis et pupillae) 6.microcoria-congenital miosis Occurs due to malformation of dilator pupillae muscle Can be associated with microcornea,lens subluxation, iris atrophy and glaucoma
  • 60. Posterior chamber  Develops as a slit in the mesenchyme posterior to the developing iris and anterior to the developing lens  Anterior and posterior communicates when the pupillary membrane disappears and the pupil is formed  Aqueous humor fills these two chamber
  • 61. Embryogenesis-Posterior segment Retina  Optic nerve  Vitreous  Choroid  Sclera  Vascular system
  • 62. Retina-originates from ectoderm  Neurosensory retina- originates from the inner layer of neuroectodermal cell of optic cup  Retinal pigment epithelium- Originates from the outer neuroectodermal cell of an optic cup
  • 63. Neurosensory layer-1st month(3-4 rows of cells)  Anterior 1/5th – forms the posterior surface of developing ciliary and iris  Posterior 4/5th forms the primordial sensory retina  Mitotic cellular differentiation at primordial retina forms two 2 distinct layers by 7th week  Outer 2/3rd –primitive nuclear zone has rows of nucleated cells which will forms neural cells  Inner 1/3rd - marginal zone has cells devoid of nucleus which will form nerve fiber layers)
  • 64. Neurosensory(NSR) retina  NSR begins to develop from outer primitive nuclear zone(PNZ)  Cellular proliferation of PNZ forms nuclear and glial cells which are organized as 2 distinctive zones 1. Outer neuroblastic layer(forms photoreceptors) 2. Inner neuroblastic layer(Ganglion cell layers) 3. Two neuroblastic layer are seperated by transient nerve fiber layer of Chievitz which become inner plexiform layer by 9th week gestation Primitive nerve fiber
  • 65. NSR formation…ctn…  Differentiation of outer neuroblastic layers occurs(ONL)by 5th week and form photoreceptors(rods and cones)  Cellular differentiation of ONL also forms bipolar, amacrine, horizontal cells and form inner nucleated layers of retina  Ganglion cell appears in inner neuroblastic layers and form ganglion cell layer  Axons from ganglion cell develops at 6th week and form primitive nerve fiber layers
  • 66. Retina-cells and synapses formation Optic cup Primitive nuclear zone Inner marginal zone forms nerve fiber layers Inner neuroblastic layer Outer neuroblastic layer Primitive neurosensory retina
  • 67.  Cellular proliferation and melanogenesis of outer wall of optic cup begins by 6th week and forms retinal pigment epithelium  By 15 week gestation all cells types , synapses and intercellular junction of neurosensory retina are formed  Fovea is formed by thinning of ganglion and inner nucleated layer by 24 weeks
  • 68. Retina by 5th week  Retinal pigment epithelium developed from outer layer of an optic cup  Outer segment- photoreceptors  Outer nucleated layers retina  Outer plexiform layers  Inner nucleated layers  Inner plexifor layers  Ganglion layer  Nerve fiber layer Derived from outer neuroblastic layer Derived from inner neuroblastic layer
  • 69. Optic nerve  Develops from optic stalk(connection between optic vesicle and forebrain)  Initially optic stalk has two layers 1. Inner neuroectodermal cells layer 2. Outer undifferentiated neural crest cells layer
  • 70. Optic nerve formation Late in 6th week, cells of inner layer of optic nerve degenerates and become vacuolated Nerve fibers (axons) from the ganglion cells migrates through the vacuolated space of optic stalk By 33 weeks it establishes an adult type optic nerve of 1.1 million of axons Few cells of inner layer differentiated into glial cell which forms lamina cribosa by 8th week.  Outer neural crest cells differentiates into (1)pia, (2)arachnoid and (3)dura matter which form optic nerve sheath by 4th month
  • 71. Optic nerve Ganglion cell layer Axons from ganglion cells Optic disc Optic nerve
  • 72. Optic anomalies 1.Morning glory disc anomaly Appears as funnel shaped excavation of the posterior fundus that incorporates the disc. Occurs due to abnormal closure of embryonic fissure 2.Coloboma of optic nerve. May occurs as a part of chorioretinal coloboma or solitary abnormality Due to failure of embryonic fissure to close Can be associated with systemic abnormalities-CHARGE association 3.
  • 73. Formation of vitreous  Develops between lens and optic cup  Mostly derived from mesoderm with minimal contribution from ectoderm  Formation of vitreous occurs in three stages ; ❶ Primary vitreous ❷Secondary vitreous ❸Tertiary vitreous
  • 74. Primary vitreous-1st month of gestation  Network of delicate cytoplasmic process which occupy the space between lens vesicle and inner layer of optic cup  It is composed of fibrils (ectoderm) and mesenchymal cells(mesoderm) which constitutes primary vitreous  Supplied by hyaloid vessels and its branches
  • 75. Secondary vitreous- 2nd month of gestation  By 2nd month the hyaloid system regresses and primary vitreous cell differentiates into hyalocytes which synthesis type 11 collagen and hyaluronic acid which constitutes secondary vitreous  2nd vitreous is avascular gel like substances occupying the space between primary vitreous and retina  By 5th -6th month primary vitreous and Hyaloid vessels undergoes atrophy.  Atrophied hyaloid vessels become hyaloid cannal which remain throughout the life as Cloquet canal Primary vitreous
  • 76. Tertiary vitreous-3rd month  It is Formation of zonular fiber between the ciliary body and lens capsule  Collagen fibrils synthesized by ciliary epithelium becomes more condensed and extends to the lens equator and become zonular fiber of lens which constitutes the tertiary vitreous
  • 77. Persistent hyperplastic primary vitreous(PHPV)  Presents as leukocoria-white pupillary reflex  Its occurs due to failure of primary vitreous and hyaloid vessels to regress  None hereditary and not associated with systemic defects.
  • 78. Choroid  Vascular endothelium and the haemopoietic cells of choroid are derived from endoderm  Choroidal stroma ( vascular pericytes, smooth muscles, melanocytes and collagenous components) of choroid are derived from ectoderm.  Choroidal development is associated with the condensation of neural crest cells around the optic cup
  • 79. Choroid..cntn  Differentiation of neural crest cells form choroidal stroma by the end of 3rd month gestation  Endothelium line blood vessels appears in the choroid stroma and forms choriocapillary  By 4the week Choriocapillary begins to differentiate and by 2nd month it anastomosis with short ciliary artery  By 8th month final arterial circulation of choroid is established after anastomosis with vessels of ciliary body and iris
  • 80. Sclera  Sclera is mostly ectodermal (neural crest) in origin, however posterior region are mesoderm in origin  Sclera begins to develop by condensation of mesenchymal cells around the anterior rim of optic cup  Mesenchymal cells proliferates and deposits glycosaminoglycans, collagen and elastin fibrils and forms stroma of sclera  By 5th month sclera is relatively well formed
  • 81. Vascular system of eye- overview  Arterial wall has three layers; 1. Tunica adventitia(connective tissue) 2. Tunica media(smooth muscle layer) 3. Tunica intima( endothelium)  Tunica adventitia and tunica media of ocular vessels are derived from neural crest cells(ectoderm)  Tunica intima is derived from endoderm
  • 82. Primitive orbital vessels  During early embryonic life untill 8th month, the developing ocular structure is nourished by three transient vessels originating from internal carotid artery; A.Ventral ophthalmic artery B. Dorsal ophthalmic artery F. Stapedial artery  Ventral artery later atrophy and only a portion remain as long posterior nasal ciliary artery  Dorsal ophthalmic artery become definitive ophthalmic artery  Stapedial artery becomes Middle meningeal artery Internal carotid artery
  • 83. Primitive ocular vessels Embryonic intraocular vasculature system has two components; 1.Anterior system- supplies anterior segment  formed in iris and pupillary membrane  formed by the branches of ophthalmil artery- anterior ciliary artery and posterior long ciliary artery 2.Posterior system- supplies posterior segment  formed within the vitreous  formed by hyaloid vascular system
  • 84. Anterior artery system  Anterior artery system is formed by posterior long,short ciliary artery and anterior ciliary artery which are the branches of dorsal opthalmic artery  Anastomosis of ciliary arteries forms major arterial circle at the root of iris  Vascular twigs from major arterial cicle and annular vessels forms the pupialiary arcade  With the disappearance of pupillary membrane pupilliary arcade remain peripherally as minor artery circle which supply iris Posterior ciliary artery Anterior ciliary artery
  • 85. Posterior arterial system Hyaloid artery nourishes the developing eye globe until the 8th month of gestation Hyaloid artery is the branch of primitive dorsal ophthalmic artery Later the Hyaloid artery regresses and become central retinal artery Atrophied ventral artery Dorsal artery
  • 86. Hyaloid system….  As the optic vesicle develops there is incomplete folds in its inferior portion of cup and stalk called embryonic fissure  Embryonic fissure allows hyaloid system to be incorporated within the eye.  In 3rd week Hyaloid artery enters the embryonic fissure of optic stalk.  With the fusion of fissure the hyaloid system are enclosed within the eye
  • 87. Clinical application  Failure to close embryonic fissure causes colobomatous deformaties of an iris, choroid, retina and optic nerve
  • 88. Hyaloid system  Branches of the hyaloid artery supplies developing lens, vitreous, optic nerve  Anastomosis of branches of hyaloid artery forms 3 arterial arcades calledTunica vasculosa Lentis 1.Anterior vascular capsule 2.Capsulopupialary portion 3.Posterior vascular capsule Valsa hyaloida propria(small capillary branches) Hyaloid artery
  • 89. Retinal circulation  By 4th month the hyaloid artery bud of to from central retinal artery  Hyaloid artery system atrophy and regresses in 3rd trimester  Retinal artery vascularizes the retinal  Nasal retina completes vascularization prior to temporal retina  By 8th month all retinal part are vascularized except for portion of peripherals temporal retina which completes 3 months after birth
  • 90. Retinal circulation  Atrophied hyaloid system  Retinal vessels buds from hyaloid artery and vascularizes retina  Vascularization reaches nasal ora serrata by 8th month and temporal ora serrata by 2 month after birth
  • 91. Retinopathy of prematurity  Ischemia triggers abnormal vessel formation called neovascularization-retinopathy of prematurity  Premature baby has incomplete vascularization of retina  Hyperoxia(supplementary oxygenation) causes vasoconstriction  Vasoconstriction causes ischemia in the incompletely developed retinal periphery
  • 92. Summary-Derivatives Ocular structures Derivatives Cornea Ectoderm Ectoderm Ectoderm and neural crest cells Vitreous EctodermCiliary body Neural crest cell(ectoderm)Trabecular meshwork Lens Iris Choroid ectodermRetina Ectoderm and mesoderm ectodermOptic nerve Ectoderm & mesodermSclera Ectoderm Mesoderm & ectodermOcular vessels
  • 93. Human eye at birth and after birth Eye grows rapidly during first 2 years of life until puberty  Most young children are hyperopic of 3.0 D because of less axial length of eye( at birth 17mm, adult 24mm)  Corneal diameter is 9.5-10.5 at birth and 12 mm in adults  Radius of corneal curvature is 6.6-7.4 mm at birth and 7.4-8.4 in adults
  • 94. …………continue Newborn has miotic pupil because dilator pipillae muscle is not well form at birth Visual development Pupillary light reflux-present after 31 week of gestation Blink reflex to light- several days after birth 6 weeks-maintain eye contact and react with facial expression 2-3months –preferential to bright objects
  • 95.
  • 96. References 1. American Academy of Ophthalmology (BCSC-section 2-fundamentas and principles of ophthalmology BCSC-section6-pediatric ophthalmology) 2.Langmans medical embryology 3.Oxford Text Book of ophthalmology 4.Internet resources