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EMBRYOLOGY OF
EYE
Nitin J Renge,
EYEBALL
 Cystic,near to roof & lateral wall,Albate spheroid
 Diamensions~Diameters AP 24mm,Horizontal
23.5mm,Vertical 23mm,Circumferance 75mm,Volume
6.5ml,Weight 7 gm
 Two poles~Anterior & Posterior
 Three Equators~Geometric,Anatomical,Surgical
 Three Axes~Optical,Visual,Fixation
 ThreeVisual angle~Alpha,Gamma,Kappa. Only Kappa
can be measured
 Three coats~Outer fibrous,MidVascular,Inner Nervous
 Two Segments~Anterior & Posterior
 Two Chambers~Anteror & Posterior
Introduction
The eyeball and its related structures are derived from
following Four primordia ;
1. Neuroectoderm~outgrowth from procencehalon ,optic
vesical
2. Surface Ectoderm~lens placode and surrounding
accessory ocular structures
3. Mesodem~surrounding optic vesicle
4. Visceral mesodem of maxillary process
Derived from germ layers
 Ectoderm(2st)
 Mesoderm(3rd)
 Endoderm(1nd)
First evidence of primitive EYE during 3rd week(day 22)of
gestation,embryo~2mm length with 8 pairs of somites
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
epithelium,HOX7.1-
ciliarybody)
Transient
population of
pluripotent cells,
originated from
neuroectoderm
which latter
transforms into
mesenchymal cell
PAX6~KeyregulatorygeneforEYEdevelopment
prechordalplate~circularlocalizedareaofcolumnar
endodermal cells,futuresiteofmouth
FGF,CHX10~regulateneural(inner)retina
TGF-B,MITF~regulatepigmented(outer)retina
PAX6,SOX2,LMAF,PROX1-responsible forlenscrystallin
SIX3~actbyinhibitingcrystallingene
BMP-4~secretedbyopticvesicle,upregulateSOX2,LMAF
GASTRULATION-early 3rd week
 formation of three germinal layers
 Begins with primitive streak by 15th day
 Primitive streak~visible as a narrow groove with
slightly bulging regions on either side in median
plane caudally on dorsal aspect of embryonic
disc with slightly elevated area on cephalic
end,primitive node.
 Epiblast cell migrates to primitive
streak,become flask shaped and detach,migrate
below epiblast
 That replace hypoblat form endoderm and then
form mesoderm.Remaining epiblast form
GASTRULATION-beginning 3rd week
Primitive streak
Gastrulation-eaqrly 3rd week
Bilaminar embryonic disc with
Migrating epiblastic cells
Gastrula with three germ
layers
Neuraltion and neural tube formation
 Neural tube is an important primitive structure from
which ocular primordia-the optic vesicle, the
progenitor mesenchymal cell (from neural crest) and
neural tissue develops
 Begins as notochord develops,it induces overlying
embryonic ectoderm in midline to thickened forming
Neural plate(16 day of gestation) and that ectodem
called neuroectodem
 Neural plate form Neural groove on 18 day of
fertilization and elevation of two side of neural groove
forms neural fold,adjacent neural plate part form
neural crest and ultimately fold fuses to become
neural tube(22 day) and neural crest cells
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
groove
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
(procencehalon), midbrain and hindbrain
 Primitive eye originates as Optic primordia,thickening
area on either side of midline on neural plate that
destined to form procencehalon (venterolateral region
of primitive forebrain)
Formation of optic and lens vesicle
 Begins with the optic primordia that depressed to
form optic sulcus then wall of optic sulcus deepens
and wall of procencephalon overlying sulcus bulge to
form Optic vesicle,proximal part become constricted
and elongated to form optic stalk
 With the formation of optic vesicle(25th day of
gestation) it induce surface ectodermal cells,in contact
laterally,thicken to form Lens Placode at 27 day of
gestation(embryo 4-4.5mm)
 Lens Placode convert into LensVesicle
 LensVesicle seprate from surface ectoderm at 33 day
of gestation
By end of 3rd week gestation
 Three primordial structure are
formed:
1. Lens placode
2. Optic vesicle
3. Mesoderm surrounding
the optic vesicles
Optic cup formation
 During Fourth week(embryo-7.6-7.8mm) of gestation
OpticVesicle converted to Optic cup by differential
growth of wall of OpticVesicle
 Margin of Optic cup grow over lens vesicle from upper
and lateral side but such growth doesn’t occur from
inferior side forming Choroidal or Embryonic fissure
 Choroidal Fissure closes by 6th -7th week of
gestation,when failsTypical Colobomata result
 By 7th week of gestation,most basic structure of eye
are present
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
includecrystallinelenssuspendedbyzonulesandstructure
anterior toit
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
equatorial cell serves as
progenitors for 2ndary lens
fibers layed concentrically
throught life
Forms primary lens fiber
filled with protein crystalline
- embryonic nucleus
 Cells of posterior wall lengthens and form elongated
fiber that projects into the lumen and specific lens
protein(crystalline) are synthesized make them
transparent,nuclei disappears
 Posterior cell contributes for most of the growth of lens
for first 3 month-preserved as compact zone of lens,
embryonic nucleus.
 From 3rd month the anterior progenitor
cells proliferates and produce 2ndary lens
fibers also called fetal nucleus upto 8th
month of gestation
 In 3rd month inner most fibres 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
formY shape suture anteriorly and inverted
Y posteriorly & complicated dendritic
pattern is observed in infantile and adult
nucleus as growth of lens fiber assymetric
following birth
Lens~8.8-9.2 mm diameter
 At birth it weighs 65mg (adult at 80 yr-258mg)
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
tissue migration from
surface ectoderm
Occurs due to spontaneous
absorption of developing
lens
2.Lenticonus and lentiglobus- localised cone
shape or spherical deformity of lens surface
Associated with Alports syndrome-X-
linked disease(lenticonus anterior)
characterized by defective genes for
production of type 1V collagen
Lens anomalies
Limited to either Embryonic or Foetal Nucleus
Most are Idiopathic
Herediatery-AD(most common),AR,X linked
Genetic a & metabolic disorders-Down syn,
marfans syndrome,galactosaemia etc.
Maternal infection and toxicity- rubella(during 1st
trimester), CMV, varicella, radiation,steroids,
thalidomide , toxoplasmosis etc.
Lamellar (zonular) Cataract~most common,
50%,Involve Foetal Nucleus.
4.Congenital cataract-etiology
3.Lens coloboma-
flattening/notching(lower quadrant of
equator) 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
Cotn….
 Congenital Ectopic Lentis~displace lens from normal
position(patellar fossa)
A. Simple ectopic lentis-Bilateral,symmetric,upwards
AD inheritance
B. Ectopic lentis et pupillae
C. Ectopic lentis with systemic anomalies
 Marfan’s Syndrome-AD,displace upward and temp
 Homocystinuria-lens subluxated downward and
nasally
 Microspherohakia~lens spherical & small in size,
occur isolated or feature of syndrome e.g.Weil-
Marchesani Syndrome or Marfan syndrome
Development of cornea-begin at 40th day
of gestation & by 5-6th month atain almost adult app
 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(Neural crest derived) migrating
towards the corneal epithelium.
 1st mesenchymal wave forms the
corneal &Trabecular endothelium .
 Desment’s membrane is derived
from the basal lamina of
endothelium
 Corneal Nerve present by 5th month
of gestation
 Foetal Cornea very Hydrated
compare to Adult So translucent
rather than transparent
Ctn…
 2nd mesenchymal wave
migrates between epithelium
and endothelium and forms
keratocytes or fibroblast
 The keratocytes synthesis type 1
collagen fibers and
proteoglycans(matrix) which are
organized as lamellae to form
stroma of cornea
 Bowman’s layer~condensation
of superficial accellular part of
stroma(after 4th month & fully
develop at birth)
Corneal derivatives
 Diameter at birth –10 mm( 9.5-10.5mm)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 horizontal diameter is less than 10mm
since birth
2.Megalocornea
Corneal diameter more tha 12mm at birth or more
than 13mm after 2 years
 Disorder of 2nd wave mesenchymal migration
 90% bilateral & cornea whole or sometimes only
periheral cornea affected
 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.
 Causes of CongenitalCloudy Cornea~Sclerocornea,tear
in descement membrane,ulcer,metabolic conditions
(STUMED)
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
 Non inflammatory,Bilateral 85%,usually start at puberty & progress
slowly
 Defective Synthesis of Mucopolysaccharide & collagen tissue
5.keratoconus-
Condition in which central cornea assume a conical shape
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
&Trabecular endothelium, 2nd waves forms Corneal
stroma & Pupillary membrane & 3rd wave forms Iris
stroma
 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 appears- 3rd Month of Gestation
Anterior chamber and angle formation
~anterior chamber depth determined genetically with Dominant
Inheritance
1stMesenchymal wave
form corneal &
Trabecular
endothelium
2nd wave forms
pupillary membrane&
Corneal stroma
3rd wave forms
Iris Stroma
Primitive
anterior
chamber-slitlik
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(1st wave) origin- forms
trabecular meshwork
 Schlemm canal develops from small plexus
of venous canaliculi of endodermal origin
and forms uveoscleral outflow/tract.
 Schlemm canal appears in 4th month of
Gestation
 Completion of Ant.Chamber Angle
formation~8th month of Gestation.
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
range 2.5-4.4)
 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
 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(CB)-ctn..
 CB begins to appear at 9th week of gestation
 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 70-75 ciliary
processes(fully form in 4th month)
 At 10 week mesenchymal cells get condensed
at its anterior surface to form the stroma of
ciliary body
 At 12 weeks there is Myofillament proliferation
of mesenchyme 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
 Zonules~Begin to develop
at 10th week and by 5th
month reach 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
Iris epithelium-end of 3rd month
 Pupillary membrane formed by
condensation 2nd wave
mesenchymal cell in early 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
 Iris fully developed by 5th month
 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
 Dilator Pupillae poorly
developed & doe not reach
adult proportions untill about
5th year of age.
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 6th or 7th week of
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
Malfoamation of iris sphincter muscle
Sphicter Muscle of the Pupil is fully differentiated by 6th
month of gestation
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 Neuroectoderm
 Neurosensory retina-
originates from the inner layer
ofneuroectodermal cell of optic
cup
 Retinal pigment epithelium-
Originates from the outer
neuroectodermal cell of an optic
cup
Neurosensory layer-1st month
 Anterior 1/5th – forms the posterior
surface of developing ciliary and iris
 Posterior 4/5th forms the primordial
sensory retina
 Single layer epithelium with ext &int
basement mem
 Proliferates to forms two 2 distinct
zones by 4th-5th week(35th day)
 Outer 2/3rd –primitive nuclear zone has
rows of nucleated cells which will
forms neural cells-Outer primitive
zone or Nuclear zone or germinal epi
 Inner 1/3rd- Inner 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) with 8-9 row of nuclei
 Mitotic Cellular proliferation of PNZ forms 2 distinctive
layers by 6th-7th wks
1. Outer neuroblastic layer(forms photoreceptors) forms rods
&cones,biolar cells &horizontal cells
2. Inner neuroblastic layer(Ganglion cell layers) forms ganglion
cells,muller’s cell &amacrine cells
3. Two neuroblastic layer are seperated by transient nerve fiber
layer of Chievitz which become inner plexiform layer by 10.5th
week gestation
NSR formation…ctn…
 Differentiation of outer neuroblastic layers occurs(ONL)by
10th-12th week & form Bipolar & Horizontal cells &
photoreceptor cells (rods and cones)
 Differentiation Inner neuroblastic layers and form
ganglion cell layer &layer of amacrine &muller cells(first
inner nuclear layer)
 Axons from ganglion cell develops at 10th-12th week and
form primitive nerve fiber layers
 A new intermediate nuclear layer,inner nuclear layer
identified by 4th month in posterior pole retina contains
biolar &horizontal cells also
 Thus differentiation of Retinal Layer starts during 6th week of
gestation & by 5th&1/2 month of gestation all layer i.e 10 layer of
adult Retina are recognizable
 Cellular proliferation and melanogenesis of outer wall of
optic cup begins by 6th week and forms retinal pigment
epithelium(RPE)
 Initially RPE is mitotically active pseudostratified
columnar ciliated epithelium cilia disappear as
melanogenesis commence & mitotic activity ceases by
birth
 Mature RPE~hexagonal shape,homogenous in size &
simple Cuboidal eithelium
 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 (7th month) of gestation
 Outer 4 layer of retina get nutrition from Choroidal vessels
& Inner 6 layer from Central Retinal Artery
Some imp landmark in Retina Development
 Synaptogenesis~in Cone pedical occur at app.4th month &
in Rod sherules at app.5th month
 Photoreceptor outer segment formation commence
arround 5th month
 Horizontal cell become distinguishable arround 5th month
 Microglia (resident tissue microhages) invade retina via
retinal vasculature by 4th month & subretinal space by 10th
week onward
 Terminal expansion of muller cells beneath inner limiting
membrane mature arround 4.5 months
 Macular area~begin to differentiate at 11th wk of
gestation, development delayed upto 8th month of
gestation ,differentiate upto 4th-6th month after birth.
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 app.1.2 million of axons
Few cells of inner layer differentiated into glial
cell which forms lamina cribosa by 8th week.
Myelination~begin from chiasma at 7th
month,proceeds distally & reach Lamina
Cribrosa just before birth and stop there
In some cases myelination extend upto
arroundOptic disc ~Cong. Opaque nerve fibre
 Outer neural crest cells differentiates into (1)pia, (2)arachnoid and
(3)dura matter which form optic nerve sheath by 4th month
Cong anomalies of Retina & Optic nerve
1. Congenital Retinoschisis~x-linked recessive,
associated with stellate pattern at fovea & occasional
vitreous haemorrhage
2. Norries’s disease~x-linked recessive, retrolental mass
with elongated ciliary rocesses with retinal
detachment.Associated with mental retardation
3. Incontinentia pigmenti~ ass. with proliferative retinal
vascular abnormalities,total retinal
detachment,cataract,RPE changes
4. Familial exudative vitreoretinoathy
5. Congenital retinal folds
6.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(EF)
 Disc has central excavation surrounded by elevated
rim of pink neuroglial tissue with vessel emerging
radially as spokes in all directions
 Sometimes remnant of sheath of hyloid vessel form
Bermeister papilla
7.Coloboma of optic nerve.
 May occurs as a part of chorioretinal coloboma or
solitary abnormality d/t EF fail to close
 Can be associated with systemic abnormalities-
CHARGE association~coloboma,heart disease
atresia choanae,retarded gwth,genital hyolasia,ear
anomalies with or without deafness
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~ Mixed ectodermal &
mesenchymal origin, develop between 3rd-9th wk of
gestation
❷Secondary vitreous~Neuroectodermal in origin,
begin to develop arround 9th wk
❸Tertiary vitreous ~Neuroectodermal in origin,
develop during 4th month gestation
Primary vitreous-1st month of gestation
 Network of delicate cytoplasmic
process which occupy the space
between lens vesicle and inner
layer of optic cup
 Surface ectodermal element
surround lens during invagination
thought to contribute primary
vitreous so mixed origin
 It is composed of fibrils (ectoderm)
and mesenchymal cells(mesoderm)
which constitutes primary vitreous
 Supplied by hyaloid vessels and its
branches so it is vascular
Secondary vitreous- 2nd month of gestation onward
(arround 9th wk)  By 2nd month the hyaloid system regresses
and primary vitreous cell differentiates into
hyalocytes which synthesis type 2 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,
regress from perihery to centre &
regration stop at optic disk leaving
central retinal artery
Atrophied hyaloid vessels become hyaloid
cannal which remain throughout the life
as Cloquet canal, from optic nerve head
to posterior surface of lens.
Primary vitreous
Tertiary vitreous-4th month
 Developed from Neuroectoderm in the ciliary region
during 4th month of gestation
 Represented byVitreous base & ciliary zonules
 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
 Primary & secondary vitreous
remain in contact with posterior
lens casule as hyaloidcasular
ligaments
Persistent hyperplastic primary vitreous(PHPV) or
persistent foetal vasculature(PFV)
 Presents as leukocoria-white pupillary reflex
 Its occurs due to failure of primary vitreous
and hyaloid vessels to regress
 Severity range from pupillary strands &
mittendrof’s dot to dense retrolenticular
membrane &/or retinal detachment
 Two tyes 1)Anterior PFV 2)Posterior PFV
 Prognosis of Posterior PFV is poor
 Insufficient level ofVitreous Endostatin
may be pathogenesis
 Normal retinal development required for
proper vitreous biosynthesis(some str.
Component synthesized by Muller Cells)
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 inner vascular layer of mesenchyme
that surround optic cup(Neural Crest)
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,6th wk completely form and by 2nd
month it anastomosis with short ciliary artery
 By 5th month all layers of Choroid now visible and
melanocyte appear in it’s external portion
 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
 Process Starts at Limbal Equatorial region
(future site of extraocular muscle
insertion) arround 7th wk of gestation
 By 5th month sclera is relatively well or
complete formed
Vascular system of eye
 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
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 ophthalmic artery- seven anterior
ciliary artery and two long posterior 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 two
long posterior,10-20 short ciliary artery
and 7 anterior ciliary artery which are
the branches of dorsal opthalmic artery
 Anastomosis of long posterior ciliary
arteries and anterior ciliary arteries
forms major arterial circle at the root of
iris
 Vascular twigs from major arterial cicle
and annular vessels forms the pupillary
arcade
 With the disappearance of pupillary
membrane pupillary 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 emerges in 5th week of gestation
 Later the Hyaloid artery regresses and become central
retinal 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 5th week Hyaloid artery enters
the embryonic fissure of optic
stalk.
 With the fusion of fissure the
hyaloid system are enclosed
within the eye
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 by 9th wk
1.Anterior vascular capsule
2.Capsulopupillary 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 begin to atrophy and regresses
in 3rd month of gestation
 Retinal artery vascularizes the retina by giving four
branches two for temporal and two for nasal side,
supplies inner six layer of retina
 Nasal retina completes vascularization prior to
temporal retina in 7th month of gestation
 By 9th month all retinal part are vascularized except
for portion of peripherals temporal retina
 Retina also well developed nasal side before temporal
Retinal circulation
 Atrophied hyaloid system
 Retinal vessels buds from
hyaloid artery and
vascularizes retina
 Vascularization reaches
nasal ora serrata by 7th
month and temporal
periphery by 9th month
Retinopathy of prematurity
 ROP associated with systemic abnomalities as anaemia,BPD,
cardiac defect,NE,IVH,cerebral palsy &neurodevelomental delay
 Premature baby has incomplete
vascularization of retina
 Hyperoxia(supplementary oxygenation)
causes vasoconstriction
 Vasoconstriction causes ischemia in the
incompletely developed retinal
periphery
 Ischemia trigger abnormal vessel
formation called neovascularization-
retinopathy of prematurity
 ROP has five stages &VEGF has
important role in pathogenesis
Accessory ocular structures
 EYELIDS~ start at 6th- 7th wk of IUL,margin of two lids
unite with flimsy tissueby 9th wk & separate 5th month
of IUL(uto 26th-28th wk)
Both eyelid formed by reduplication of surface ectoderm
1.Lower eyelid-Formed from maxillary process &
connective tissue & tarsal plate from visceral
mesoderm of Maxillary process
2.Upper eyelid-Formed from lateral and medial aspect
of frontonasal & connective tissue & tarsal late from
periocular mesodem derived from neural crest
Skin of eyelids and it’s derivatives cilia,cojunctival &
Tarsal Gland-from Ectodermal cell from lid margin.
Continue……….
 Conjunctiva~ from surface ectoderm
 Lacrimal apparatus~
1.Lacrimal Gland-from 8 cuneiform eithelial bud from
superolateral side of conjunctival sac, by end of 2nd
month.At term still undeveloped & tear not formed
2.Lacrimal Sac,Nasolacrimal duct and canaliculi-
developed from ectoderm of nasolacrimal groove
Nsolacrimal duct becomes completely patent only
after birth
 Extraocular Muscles~are some of few periocular
tissues that are not neural crest origin,differentiated
from prechordal mesenchyme,start in 5th-6th wk
(LR,SR,LPS-5th wk;SO,MR-6th wk & then IO,IR)
Conti…..
 Orbit~derived above from mesenchyme encircles
optic vesicle,below & laterally from maxillary
processes,medially by frontonasal process &
behind by pre-and orbitoshenoid.
Orbit Bone Formed by membraneous ossification
Bone differentiated during 3rd month
 InitiallyOptic Axis direct laterally, later they
directed anteriorly
 At Birth Orbit is hemispherical & more divergent
(50 degree) as compare to adult-45 degree
Eyeball reachesAdult Size by 3 year of age
Orbit alteration in shape & grows until Puberty
Congenital anomalies of Eyelids
1. Eicanthal fold
2. Telecanthus
3. Epibleharon
4. Blepharophimosis
5. Eurybleharon
6. Coloboma of lid~Upper lid at middle & lateral third
seen in Goldhar’s Syndrome, Lower lid seen in
Teacher collins Syndrome with hypolasia of lower lid
7. Ankylobleharon
8. Cryptophthalmos~failure of sepration of lid during 4th
to 6th wk of IULthus lids fail to develop & skin passes
from eyeball to cheek hiding eyeball
Congenital anamolies of conjunctiva
1. Congenital cystic lesions~ rare,include congenital
corneoscleral cyst & cystic form of epibulbar dermoid
2. Dermoid ~common congenital tumour,occur at
limbus,solid white masses,firmly fix to cornea
3. Lipodemoid (epibulbar dermoid)~at limbus 0r outer
canthus,movable subconjuntival mass
4. Naevi or Congenital moles~common pigmented
lesions,mostly near limbus,appears in early childhood
& may increase in size at puberty or during
pregnancy
Congenital anomalies of lacrimal
apparatus
1. Congenital NLD block~in 80-90% residual membrane
spontaneously dissolve within 2-4 month after birth
2. Congenital lacrimal Fistula (lacrimal anlage duct)~
fistula open on skin below and medial to lower
punctum , may associated with congenital NLD block
3. Punctal Atresia~Imperforated punctum,
presumed location of punctum identified as a
shallow dimple at appropriate site
Human eye at birth and after birth
 Newborn are hypermetropic by 2-3D because of
less axial length of eye( at birth 16.5mm, adult
24mm,70% of adult attained by 7-8 years)
 Corneal diameter is 10mm at birth and 11.7mm in
adults is attained by 2 years of age
 Radius of corneal curvature is 6.6-7.4 mm at birth
and 7.4-8.4 in adults
 Retina fully differentiated at birth except Macula,
differentiate in first 4 month with foveal reflex
 General picture of fundus as adult after 6th month
…………continue
 Newborn has miotic pupil because dilator pipillae muscle
is not well form at birth.Reach adult proportion~at
approximately 5th year age
 Lens Spherical at birth
 Orbit is more divergent (50) as compared to adult (45)
 Anterior chamber is shallow and angle is narrow
 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
 Conjugate fixation~become established by 6th month
References
1.Anatomy and Physiology of eye-2nd edition,Dr.A K
Khurana
2.Ophthalmology,third edition,Dr.A K Khurana
3.Langman’s Medical Embryology,11th edition
4.Parsons Diseases of eye,22nd edition
5.Yanhoff’s Ophthalmology,4th edition
6.Essential of Embryology and Birth Defect,7th edition
7.Internate Resources
Thank
you

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Eye 5;1

  • 2. EYEBALL  Cystic,near to roof & lateral wall,Albate spheroid  Diamensions~Diameters AP 24mm,Horizontal 23.5mm,Vertical 23mm,Circumferance 75mm,Volume 6.5ml,Weight 7 gm  Two poles~Anterior & Posterior  Three Equators~Geometric,Anatomical,Surgical  Three Axes~Optical,Visual,Fixation  ThreeVisual angle~Alpha,Gamma,Kappa. Only Kappa can be measured  Three coats~Outer fibrous,MidVascular,Inner Nervous  Two Segments~Anterior & Posterior  Two Chambers~Anteror & Posterior
  • 3.
  • 4.
  • 5. Introduction The eyeball and its related structures are derived from following Four primordia ; 1. Neuroectoderm~outgrowth from procencehalon ,optic vesical 2. Surface Ectoderm~lens placode and surrounding accessory ocular structures 3. Mesodem~surrounding optic vesicle 4. Visceral mesodem of maxillary process Derived from germ layers  Ectoderm(2st)  Mesoderm(3rd)  Endoderm(1nd) First evidence of primitive EYE during 3rd week(day 22)of gestation,embryo~2mm length with 8 pairs of somites
  • 6. 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 epithelium,HOX7.1- ciliarybody) Transient population of pluripotent cells, originated from neuroectoderm which latter transforms into mesenchymal cell
  • 9. GASTRULATION-early 3rd week  formation of three germinal layers  Begins with primitive streak by 15th day  Primitive streak~visible as a narrow groove with slightly bulging regions on either side in median plane caudally on dorsal aspect of embryonic disc with slightly elevated area on cephalic end,primitive node.  Epiblast cell migrates to primitive streak,become flask shaped and detach,migrate below epiblast  That replace hypoblat form endoderm and then form mesoderm.Remaining epiblast form
  • 11. Gastrulation-eaqrly 3rd week Bilaminar embryonic disc with Migrating epiblastic cells Gastrula with three germ layers
  • 12. Neuraltion and neural tube formation  Neural tube is an important primitive structure from which ocular primordia-the optic vesicle, the progenitor mesenchymal cell (from neural crest) and neural tissue develops  Begins as notochord develops,it induces overlying embryonic ectoderm in midline to thickened forming Neural plate(16 day of gestation) and that ectodem called neuroectodem  Neural plate form Neural groove on 18 day of fertilization and elevation of two side of neural groove forms neural fold,adjacent neural plate part form neural crest and ultimately fold fuses to become neural tube(22 day) and neural crest cells
  • 13. Neuraltion and neural tube formation-22th day Neural crest cell Gartrula Neural grove
  • 14. Neuraltion and neural tube formation-22th day 1.Neural plate 2.Neural groove 3.Neural tube Neural crest cell- proginater cells for mesenchymal cells Surface ectoderm
  • 15. 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 (procencehalon), midbrain and hindbrain  Primitive eye originates as Optic primordia,thickening area on either side of midline on neural plate that destined to form procencehalon (venterolateral region of primitive forebrain)
  • 16.
  • 17. Formation of optic and lens vesicle  Begins with the optic primordia that depressed to form optic sulcus then wall of optic sulcus deepens and wall of procencephalon overlying sulcus bulge to form Optic vesicle,proximal part become constricted and elongated to form optic stalk  With the formation of optic vesicle(25th day of gestation) it induce surface ectodermal cells,in contact laterally,thicken to form Lens Placode at 27 day of gestation(embryo 4-4.5mm)  Lens Placode convert into LensVesicle  LensVesicle seprate from surface ectoderm at 33 day of gestation
  • 18.
  • 19. By end of 3rd week gestation  Three primordial structure are formed: 1. Lens placode 2. Optic vesicle 3. Mesoderm surrounding the optic vesicles
  • 20. Optic cup formation  During Fourth week(embryo-7.6-7.8mm) of gestation OpticVesicle converted to Optic cup by differential growth of wall of OpticVesicle  Margin of Optic cup grow over lens vesicle from upper and lateral side but such growth doesn’t occur from inferior side forming Choroidal or Embryonic fissure  Choroidal Fissure closes by 6th -7th week of gestation,when failsTypical Colobomata result  By 7th week of gestation,most basic structure of eye are present
  • 21. 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
  • 22. Anterior segments-development includecrystallinelenssuspendedbyzonulesandstructure anterior toit Development of eye structure are mostly induced with the formation of optic vesicle and lens placode
  • 23. 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
  • 24. 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 equatorial cell serves as progenitors for 2ndary lens fibers layed concentrically throught life Forms primary lens fiber filled with protein crystalline - embryonic nucleus
  • 25.  Cells of posterior wall lengthens and form elongated fiber that projects into the lumen and specific lens protein(crystalline) are synthesized make them transparent,nuclei disappears  Posterior cell contributes for most of the growth of lens for first 3 month-preserved as compact zone of lens, embryonic nucleus.
  • 26.
  • 27.  From 3rd month the anterior progenitor cells proliferates and produce 2ndary lens fibers also called fetal nucleus upto 8th month of gestation  In 3rd month inner most fibres 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 formY shape suture anteriorly and inverted Y posteriorly & complicated dendritic pattern is observed in infantile and adult nucleus as growth of lens fiber assymetric following birth
  • 28. Lens~8.8-9.2 mm diameter  At birth it weighs 65mg (adult at 80 yr-258mg) with thickness of 3.5mm ( adult-5mm)  Lens fiber are formed throughout the human life developing into different layers of lens fibers
  • 29. Lens anomalies  ! 1.Congenital aphakia-absence of lens at birth primary aphakia Secondary aphakia(more common) Occurs due to failure of tissue migration from surface ectoderm Occurs due to spontaneous absorption of developing lens 2.Lenticonus and lentiglobus- localised cone shape or spherical deformity of lens surface Associated with Alports syndrome-X- linked disease(lenticonus anterior) characterized by defective genes for production of type 1V collagen
  • 30. Lens anomalies Limited to either Embryonic or Foetal Nucleus Most are Idiopathic Herediatery-AD(most common),AR,X linked Genetic a & metabolic disorders-Down syn, marfans syndrome,galactosaemia etc. Maternal infection and toxicity- rubella(during 1st trimester), CMV, varicella, radiation,steroids, thalidomide , toxoplasmosis etc. Lamellar (zonular) Cataract~most common, 50%,Involve Foetal Nucleus. 4.Congenital cataract-etiology 3.Lens coloboma- flattening/notching(lower quadrant of equator) 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
  • 31. Cotn….  Congenital Ectopic Lentis~displace lens from normal position(patellar fossa) A. Simple ectopic lentis-Bilateral,symmetric,upwards AD inheritance B. Ectopic lentis et pupillae C. Ectopic lentis with systemic anomalies  Marfan’s Syndrome-AD,displace upward and temp  Homocystinuria-lens subluxated downward and nasally  Microspherohakia~lens spherical & small in size, occur isolated or feature of syndrome e.g.Weil- Marchesani Syndrome or Marfan syndrome
  • 32. Development of cornea-begin at 40th day of gestation & by 5-6th month atain almost adult app  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
  • 33. Corneal embryogenesis-5th week  By early 5th week gestation there are 3 waves of mesenchymal cells(Neural crest derived) migrating towards the corneal epithelium.  1st mesenchymal wave forms the corneal &Trabecular endothelium .  Desment’s membrane is derived from the basal lamina of endothelium  Corneal Nerve present by 5th month of gestation  Foetal Cornea very Hydrated compare to Adult So translucent rather than transparent
  • 34. Ctn…  2nd mesenchymal wave migrates between epithelium and endothelium and forms keratocytes or fibroblast  The keratocytes synthesis type 1 collagen fibers and proteoglycans(matrix) which are organized as lamellae to form stroma of cornea  Bowman’s layer~condensation of superficial accellular part of stroma(after 4th month & fully develop at birth)
  • 35. Corneal derivatives  Diameter at birth –10 mm( 9.5-10.5mm)reaches adult size 12 mm by 2 years Derived from surface ectoderm Derived from mesenchyme(neural crest cell) Derived from mesenchyme(neural crest cell)
  • 36. 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 horizontal diameter is less than 10mm since birth 2.Megalocornea Corneal diameter more tha 12mm at birth or more than 13mm after 2 years
  • 37.  Disorder of 2nd wave mesenchymal migration  90% bilateral & cornea whole or sometimes only periheral cornea affected  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.  Causes of CongenitalCloudy Cornea~Sclerocornea,tear in descement membrane,ulcer,metabolic conditions (STUMED) 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
  • 38.  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  Non inflammatory,Bilateral 85%,usually start at puberty & progress slowly  Defective Synthesis of Mucopolysaccharide & collagen tissue 5.keratoconus- Condition in which central cornea assume a conical shape
  • 39. 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 &Trabecular endothelium, 2nd waves forms Corneal stroma & Pupillary membrane & 3rd wave forms Iris stroma  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 appears- 3rd Month of Gestation
  • 40. Anterior chamber and angle formation ~anterior chamber depth determined genetically with Dominant Inheritance 1stMesenchymal wave form corneal & Trabecular endothelium 2nd wave forms pupillary membrane& Corneal stroma 3rd wave forms Iris Stroma Primitive anterior chamber-slitlik space
  • 41.  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(1st wave) origin- forms trabecular meshwork  Schlemm canal develops from small plexus of venous canaliculi of endodermal origin and forms uveoscleral outflow/tract.  Schlemm canal appears in 4th month of Gestation  Completion of Ant.Chamber Angle formation~8th month of Gestation.
  • 42. 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 range 2.5-4.4)  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
  • 43. Ciliary body and iris  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
  • 44. Ciliary body(CB)-ctn..  CB begins to appear at 9th week of gestation  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 70-75 ciliary processes(fully form in 4th month)  At 10 week mesenchymal cells get condensed at its anterior surface to form the stroma of ciliary body  At 12 weeks there is Myofillament proliferation of mesenchyme and forms smooth muscles of ciliary body by 5th month  Ciliary muscle continues to develop for at least 1year after birth.
  • 45. 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  Zonules~Begin to develop at 10th week and by 5th month reach Lens
  • 46. 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
  • 47. Iris epithelium-end of 3rd month  Pupillary membrane formed by condensation 2nd wave mesenchymal cell in early 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
  • 48. 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  Iris fully developed by 5th month  pigmentation of posterior epithelial cell occurs begins at the pupillary margin at midterm , by 7th month iris is fully pigmented
  • 49. 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  Dilator Pupillae poorly developed & doe not reach adult proportions untill about 5th year of age.
  • 50. 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 6th or 7th week of 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
  • 51. Iris anomalies… 7.Conginatal mydriasis Malfoamation of iris sphincter muscle Sphicter Muscle of the Pupil is fully differentiated by 6th month of gestation 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
  • 52. 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
  • 53. Embryogenesis-Posterior segment  Retina  Optic nerve  Vitreous  Choroid  Sclera  Vascular system
  • 54. Retina-originates from Neuroectoderm  Neurosensory retina- originates from the inner layer ofneuroectodermal cell of optic cup  Retinal pigment epithelium- Originates from the outer neuroectodermal cell of an optic cup
  • 55. Neurosensory layer-1st month  Anterior 1/5th – forms the posterior surface of developing ciliary and iris  Posterior 4/5th forms the primordial sensory retina  Single layer epithelium with ext &int basement mem  Proliferates to forms two 2 distinct zones by 4th-5th week(35th day)  Outer 2/3rd –primitive nuclear zone has rows of nucleated cells which will forms neural cells-Outer primitive zone or Nuclear zone or germinal epi  Inner 1/3rd- Inner marginal zone has cells devoid of nucleus which will form nerve fiber layers
  • 56. Neurosensory(NSR) retina  NSR begins to develop from outer primitive nuclear zone(PNZ) with 8-9 row of nuclei  Mitotic Cellular proliferation of PNZ forms 2 distinctive layers by 6th-7th wks 1. Outer neuroblastic layer(forms photoreceptors) forms rods &cones,biolar cells &horizontal cells 2. Inner neuroblastic layer(Ganglion cell layers) forms ganglion cells,muller’s cell &amacrine cells 3. Two neuroblastic layer are seperated by transient nerve fiber layer of Chievitz which become inner plexiform layer by 10.5th week gestation
  • 57. NSR formation…ctn…  Differentiation of outer neuroblastic layers occurs(ONL)by 10th-12th week & form Bipolar & Horizontal cells & photoreceptor cells (rods and cones)  Differentiation Inner neuroblastic layers and form ganglion cell layer &layer of amacrine &muller cells(first inner nuclear layer)  Axons from ganglion cell develops at 10th-12th week and form primitive nerve fiber layers  A new intermediate nuclear layer,inner nuclear layer identified by 4th month in posterior pole retina contains biolar &horizontal cells also  Thus differentiation of Retinal Layer starts during 6th week of gestation & by 5th&1/2 month of gestation all layer i.e 10 layer of adult Retina are recognizable
  • 58.
  • 59.  Cellular proliferation and melanogenesis of outer wall of optic cup begins by 6th week and forms retinal pigment epithelium(RPE)  Initially RPE is mitotically active pseudostratified columnar ciliated epithelium cilia disappear as melanogenesis commence & mitotic activity ceases by birth  Mature RPE~hexagonal shape,homogenous in size & simple Cuboidal eithelium  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 (7th month) of gestation  Outer 4 layer of retina get nutrition from Choroidal vessels & Inner 6 layer from Central Retinal Artery
  • 60. Some imp landmark in Retina Development  Synaptogenesis~in Cone pedical occur at app.4th month & in Rod sherules at app.5th month  Photoreceptor outer segment formation commence arround 5th month  Horizontal cell become distinguishable arround 5th month  Microglia (resident tissue microhages) invade retina via retinal vasculature by 4th month & subretinal space by 10th week onward  Terminal expansion of muller cells beneath inner limiting membrane mature arround 4.5 months  Macular area~begin to differentiate at 11th wk of gestation, development delayed upto 8th month of gestation ,differentiate upto 4th-6th month after birth.
  • 61. 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
  • 62. 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 app.1.2 million of axons Few cells of inner layer differentiated into glial cell which forms lamina cribosa by 8th week. Myelination~begin from chiasma at 7th month,proceeds distally & reach Lamina Cribrosa just before birth and stop there In some cases myelination extend upto arroundOptic disc ~Cong. Opaque nerve fibre  Outer neural crest cells differentiates into (1)pia, (2)arachnoid and (3)dura matter which form optic nerve sheath by 4th month
  • 63. Cong anomalies of Retina & Optic nerve 1. Congenital Retinoschisis~x-linked recessive, associated with stellate pattern at fovea & occasional vitreous haemorrhage 2. Norries’s disease~x-linked recessive, retrolental mass with elongated ciliary rocesses with retinal detachment.Associated with mental retardation 3. Incontinentia pigmenti~ ass. with proliferative retinal vascular abnormalities,total retinal detachment,cataract,RPE changes 4. Familial exudative vitreoretinoathy 5. Congenital retinal folds
  • 64. 6.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(EF)  Disc has central excavation surrounded by elevated rim of pink neuroglial tissue with vessel emerging radially as spokes in all directions  Sometimes remnant of sheath of hyloid vessel form Bermeister papilla 7.Coloboma of optic nerve.  May occurs as a part of chorioretinal coloboma or solitary abnormality d/t EF fail to close  Can be associated with systemic abnormalities- CHARGE association~coloboma,heart disease atresia choanae,retarded gwth,genital hyolasia,ear anomalies with or without deafness
  • 65. 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~ Mixed ectodermal & mesenchymal origin, develop between 3rd-9th wk of gestation ❷Secondary vitreous~Neuroectodermal in origin, begin to develop arround 9th wk ❸Tertiary vitreous ~Neuroectodermal in origin, develop during 4th month gestation
  • 66. Primary vitreous-1st month of gestation  Network of delicate cytoplasmic process which occupy the space between lens vesicle and inner layer of optic cup  Surface ectodermal element surround lens during invagination thought to contribute primary vitreous so mixed origin  It is composed of fibrils (ectoderm) and mesenchymal cells(mesoderm) which constitutes primary vitreous  Supplied by hyaloid vessels and its branches so it is vascular
  • 67. Secondary vitreous- 2nd month of gestation onward (arround 9th wk)  By 2nd month the hyaloid system regresses and primary vitreous cell differentiates into hyalocytes which synthesis type 2 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, regress from perihery to centre & regration stop at optic disk leaving central retinal artery Atrophied hyaloid vessels become hyaloid cannal which remain throughout the life as Cloquet canal, from optic nerve head to posterior surface of lens. Primary vitreous
  • 68. Tertiary vitreous-4th month  Developed from Neuroectoderm in the ciliary region during 4th month of gestation  Represented byVitreous base & ciliary zonules  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  Primary & secondary vitreous remain in contact with posterior lens casule as hyaloidcasular ligaments
  • 69. Persistent hyperplastic primary vitreous(PHPV) or persistent foetal vasculature(PFV)  Presents as leukocoria-white pupillary reflex  Its occurs due to failure of primary vitreous and hyaloid vessels to regress  Severity range from pupillary strands & mittendrof’s dot to dense retrolenticular membrane &/or retinal detachment  Two tyes 1)Anterior PFV 2)Posterior PFV  Prognosis of Posterior PFV is poor  Insufficient level ofVitreous Endostatin may be pathogenesis  Normal retinal development required for proper vitreous biosynthesis(some str. Component synthesized by Muller Cells)
  • 70. 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 inner vascular layer of mesenchyme that surround optic cup(Neural Crest)
  • 71. 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,6th wk completely form and by 2nd month it anastomosis with short ciliary artery  By 5th month all layers of Choroid now visible and melanocyte appear in it’s external portion  By 8th month final arterial circulation of choroid is established after anastomosis with vessels of ciliary body and iris
  • 72. 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  Process Starts at Limbal Equatorial region (future site of extraocular muscle insertion) arround 7th wk of gestation  By 5th month sclera is relatively well or complete formed
  • 73. Vascular system of eye  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
  • 74. 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
  • 75. 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 ophthalmic artery- seven anterior ciliary artery and two long posterior ciliary artery 2.Posterior system- supplies posterior segment  formed within the vitreous  formed by hyaloid vascular system
  • 76. Anterior artery system  Anterior artery system is formed by two long posterior,10-20 short ciliary artery and 7 anterior ciliary artery which are the branches of dorsal opthalmic artery  Anastomosis of long posterior ciliary arteries and anterior ciliary arteries forms major arterial circle at the root of iris  Vascular twigs from major arterial cicle and annular vessels forms the pupillary arcade  With the disappearance of pupillary membrane pupillary arcade remain peripherally as minor artery circle which supply iris Posterior ciliary artery Anterior ciliary artery
  • 77. 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 emerges in 5th week of gestation  Later the Hyaloid artery regresses and become central retinal artery
  • 78. 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 5th week Hyaloid artery enters the embryonic fissure of optic stalk.  With the fusion of fissure the hyaloid system are enclosed within the eye
  • 79. 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 by 9th wk 1.Anterior vascular capsule 2.Capsulopupillary portion 3.Posterior vascular capsule  Valsa hyaloida propria(small capillary branches)  Hyaloid artery
  • 80. Retinal circulation  By 4th month the hyaloid artery bud of to from central retinal artery  Hyaloid artery system begin to atrophy and regresses in 3rd month of gestation  Retinal artery vascularizes the retina by giving four branches two for temporal and two for nasal side, supplies inner six layer of retina  Nasal retina completes vascularization prior to temporal retina in 7th month of gestation  By 9th month all retinal part are vascularized except for portion of peripherals temporal retina  Retina also well developed nasal side before temporal
  • 81. Retinal circulation  Atrophied hyaloid system  Retinal vessels buds from hyaloid artery and vascularizes retina  Vascularization reaches nasal ora serrata by 7th month and temporal periphery by 9th month
  • 82. Retinopathy of prematurity  ROP associated with systemic abnomalities as anaemia,BPD, cardiac defect,NE,IVH,cerebral palsy &neurodevelomental delay  Premature baby has incomplete vascularization of retina  Hyperoxia(supplementary oxygenation) causes vasoconstriction  Vasoconstriction causes ischemia in the incompletely developed retinal periphery  Ischemia trigger abnormal vessel formation called neovascularization- retinopathy of prematurity  ROP has five stages &VEGF has important role in pathogenesis
  • 83. Accessory ocular structures  EYELIDS~ start at 6th- 7th wk of IUL,margin of two lids unite with flimsy tissueby 9th wk & separate 5th month of IUL(uto 26th-28th wk) Both eyelid formed by reduplication of surface ectoderm 1.Lower eyelid-Formed from maxillary process & connective tissue & tarsal plate from visceral mesoderm of Maxillary process 2.Upper eyelid-Formed from lateral and medial aspect of frontonasal & connective tissue & tarsal late from periocular mesodem derived from neural crest Skin of eyelids and it’s derivatives cilia,cojunctival & Tarsal Gland-from Ectodermal cell from lid margin.
  • 84.
  • 85. Continue……….  Conjunctiva~ from surface ectoderm  Lacrimal apparatus~ 1.Lacrimal Gland-from 8 cuneiform eithelial bud from superolateral side of conjunctival sac, by end of 2nd month.At term still undeveloped & tear not formed 2.Lacrimal Sac,Nasolacrimal duct and canaliculi- developed from ectoderm of nasolacrimal groove Nsolacrimal duct becomes completely patent only after birth  Extraocular Muscles~are some of few periocular tissues that are not neural crest origin,differentiated from prechordal mesenchyme,start in 5th-6th wk (LR,SR,LPS-5th wk;SO,MR-6th wk & then IO,IR)
  • 86. Conti…..  Orbit~derived above from mesenchyme encircles optic vesicle,below & laterally from maxillary processes,medially by frontonasal process & behind by pre-and orbitoshenoid. Orbit Bone Formed by membraneous ossification Bone differentiated during 3rd month  InitiallyOptic Axis direct laterally, later they directed anteriorly  At Birth Orbit is hemispherical & more divergent (50 degree) as compare to adult-45 degree Eyeball reachesAdult Size by 3 year of age Orbit alteration in shape & grows until Puberty
  • 87. Congenital anomalies of Eyelids 1. Eicanthal fold 2. Telecanthus 3. Epibleharon 4. Blepharophimosis 5. Eurybleharon 6. Coloboma of lid~Upper lid at middle & lateral third seen in Goldhar’s Syndrome, Lower lid seen in Teacher collins Syndrome with hypolasia of lower lid 7. Ankylobleharon 8. Cryptophthalmos~failure of sepration of lid during 4th to 6th wk of IULthus lids fail to develop & skin passes from eyeball to cheek hiding eyeball
  • 88. Congenital anamolies of conjunctiva 1. Congenital cystic lesions~ rare,include congenital corneoscleral cyst & cystic form of epibulbar dermoid 2. Dermoid ~common congenital tumour,occur at limbus,solid white masses,firmly fix to cornea 3. Lipodemoid (epibulbar dermoid)~at limbus 0r outer canthus,movable subconjuntival mass 4. Naevi or Congenital moles~common pigmented lesions,mostly near limbus,appears in early childhood & may increase in size at puberty or during pregnancy
  • 89. Congenital anomalies of lacrimal apparatus 1. Congenital NLD block~in 80-90% residual membrane spontaneously dissolve within 2-4 month after birth 2. Congenital lacrimal Fistula (lacrimal anlage duct)~ fistula open on skin below and medial to lower punctum , may associated with congenital NLD block 3. Punctal Atresia~Imperforated punctum, presumed location of punctum identified as a shallow dimple at appropriate site
  • 90. Human eye at birth and after birth  Newborn are hypermetropic by 2-3D because of less axial length of eye( at birth 16.5mm, adult 24mm,70% of adult attained by 7-8 years)  Corneal diameter is 10mm at birth and 11.7mm in adults is attained by 2 years of age  Radius of corneal curvature is 6.6-7.4 mm at birth and 7.4-8.4 in adults  Retina fully differentiated at birth except Macula, differentiate in first 4 month with foveal reflex  General picture of fundus as adult after 6th month
  • 91. …………continue  Newborn has miotic pupil because dilator pipillae muscle is not well form at birth.Reach adult proportion~at approximately 5th year age  Lens Spherical at birth  Orbit is more divergent (50) as compared to adult (45)  Anterior chamber is shallow and angle is narrow  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  Conjugate fixation~become established by 6th month
  • 92.
  • 93. References 1.Anatomy and Physiology of eye-2nd edition,Dr.A K Khurana 2.Ophthalmology,third edition,Dr.A K Khurana 3.Langman’s Medical Embryology,11th edition 4.Parsons Diseases of eye,22nd edition 5.Yanhoff’s Ophthalmology,4th edition 6.Essential of Embryology and Birth Defect,7th edition 7.Internate Resources