2. Outline
➢ Basics
➢ Stages in development
➢ Development of eye
• Formation of :optic vesicle and optic cup
:lens vesicle
:anterior ocular structures
:posterior ocular structures
:other ocular structures
Clinical
Correlations
3. Basics
• From a single cell to a baby in 9 months, series
of developmental process occur representing an
amazing integration of increasingly complex
phenomena, the study of which is k/a
embryology
• Includes investigations of molecular, cellular &
structural factors contributing to formation of
organism
4. Stages in Development
➢ Embryogenesis : Organization & development of
primary layers of developing embryo
➢ Organogenesis : Germ layers develop into
internal organs of organism
➢ Differentiation: mechanism whereby embryonic
cells stop being flexible & turn into more mature
cells that can develop into specific tissues
4
10. Eye
• Neural tube bears series of bulges/swellings
• Initially forms 3 primary vesicles
1. Prosencephalon: Telencephalon+ Diencephalon
2. Mesencephalon
3. Rhombencephalon
• Surface ectoderm covers outside of forebrain, and
neural ectoderm lines inner surfaces of the paired
forebrain vesicles from which eyes develop
Regional Brain Development
11. Clinical Sig. Holoprosencephaly
• Failure of embryonic prosencephalon to cleave
into two cerebral hemispheres & properly divide the
orbits of eye into two cavities
• 5-6 wk
• Key findings:
➢ Cleft lip/palate(mild)
➢ CYCLOPIA(severe)
12. Development of Eye
• Considered to commence around Day-22 when
embryo has 8 pairs of somites and 2 mm in length
• Eye is derived from 3 of primitive embryonic layers:
1.Surface ectoderm & its derivative neural crest
2.Mesoderm
3.Neuroectoderm
-Endoderm does not enter in formation of eye
13. Formation of optic vesicle & Stalk
The optic sulci develop as
bilateral evaginations of
developing neuraltube
Expansion of optic sulci toward
surface ectoderm & ballooning
create optic vesicles by day 25 to
26 (embryo size, 3mm)
The optic vesicles remain attached
to,& continuous with, neural tube by
optic stalks
The expansion and ballooning that take place
in hollow optic vesicle do not occur in the stalk,
thus remains as a tubular link from cavity of
vesicle to that of diencephalon.
14. Clinical Sig. Papilloedema
• Optic vesicle → outgrowth of brain itself
• Continuity of subarachnoid space around brain with
space around optic nerve
• Any increase in intracranial pressure transmitted
through subarachnoid space to space around optic
nerve
• ↑ ICP causes:
➢ Obstruction to venous return from retina
➢ Oedema of optic disc
17. Congenital cystic Eye
• Eye fails to develop correctly in utero and is
replaced by benign, fluid-filled tissue
• Day 35,optic vesicle fails to invaginate
• The development of entire globe is arrested, &
ectodermal elements do not differentiate
Clinical Sig.
18. Formation of lens vesicle
Optic vesicle grows laterally, comes in contact with surface
ectoderm
Induces changes to form lens placode
Lens placode & adjacent cells of optic vesicle invaginate
inward to form lens pit
sinks below to form lens vesicle
separates from surface ectoderm
25
days
33
days
27
days
29
days
33
days
Lens vesicle detachment from Surface
Ectoderm is the initial event leading to
formation of chambers of eye
20. Formation of optic cup
• When lens vesicle is forming,
Optic
vesicle
Optic cup
Differential growth of walls
of vesicle
21. • Margins of cup grow over upper & lateral sides of
lens to enclose it
Not over inferior part
Choroidal /Fetal Fissure
Closes by 6th wk
Failure to fuse results
typical COLOBOMAS
Pupil
Once the fissure has closed, secretion of
primitive aqueous fluid by primitive ciliary
epithelium establishes IOP which contributes to
expansion of optic cup
22. Colobomas
• Colobomas represent an absence of tissue
• may occur anywhere along optic fissure and
can affect the iris, choroid, macula & optic nerve
Because the optic fissure closes first at equator of
eye, & then in a posterior and anterior direction,
colobomas are most frequently found at the two ends
of the optic fissure, i.e iris and optic nerve
23. Applied
• Failure or late closure of optic fissure prevents
establishment of normal fetal IOP & can therefore
result in Colobomatous Microphthalmia
Clinical Sig.
24. Changes in associated
mesenchyme
• Neural tube is surrounded by mesenchyme
• Extension of this mesenchyme also surrounds
optic vesicle
Mesenchyme
Fibrous layer
(superficial)
Sclera
Cornea
Vascular Layer
(deep)
Stroma of
uveal tissue
Mesenchyme is loose tissue
consisting stellate amoeboid
cells embedded in matrix rich in
GAGs
Derived from:
• Mesoderm
• Neural crest
25. With formation of optic cup, part of vascular
layer of mesenchyme carried into cup
through choroidal fissure
With closure, part of mesenchyme
entrapped forms hyaloid system of
vessels
At 4 months, retinal artery and vein
26.
27. The eyelids develop from surface ectoderm that gives
rise to epidermis, cilia, and conjunctival epithelium
Mesenchyme (Neural crest cell) gives rise to deeper
structures including dermis and tarsus
The eyelid muscles, orbicularis and levator,
are derived from mesoderm
.
Eyelids
28. The lid folds grow together and elongate to cover
developing eye
Upper and lower lids fuse together at approximately
10 weeks
By 6 months, glandular structures and cilia develop,
and the lids gradually separate.
30. Eyelid Coloboma
• Partial or total absence of
eyelid structures
• Results from:
➢ Failure of mesodermal
folds of lids to meet
➢ Premature separation of
lids during development
Clinical Sig.
31.
32. Cryptophthalmos
Failure of eyelids to form correctly during
development
Results in covering of globe by a continuous layer
of skin
32
Clinical Sig.
34. Eyelashes
• 1st cilia appear at lid
junction
• Hair follicles of cilia arise
on both lid margins
anteroposterior direction
DISTICHIASIS
presence of a second row of
eyelashes that arise from
meibomian glands
35. Conjunctiva
• From ectoderm lining the lids and covering the
globe
• Conjunctival glands develop as a growth of
basal cells of upper conjunctival fornix.
• Fewer glands develop from lower fornix
ADENOID LAYER
• Develops at 2-3 months of life
• Conjuctival inflammation in an infant
does not produce follicular reaction
36. Dermoids and Dermolipomas
• Dermoids are choristomas (histologically normal
tissue in an abnormal location)
• Arrest or inclusions of epidermal and connective
tissues (surface ectoderm & neural crest cells)
• a/w abnormal closure of optic fissure
• occur at :limbus (limbal dermoid),
:conjunctiva (dermolipoma)
:subcutaneously in & around orbit.
• limbal dermoids→ Corneal astigmatism
37. Goldenhar’s syndrome
• Oculoauriculovertebral dysplasia
• Neural crest cell abnormalities
• Characterized by combination of :
➢ Epibulbar dermoids
➢ Ocular coloboma
➢ Incomplete cryptophthalmos or lid colobomas,
➢ preauricular skin tags,
➢ Heart & pulmonary defects
38. Sclera
• From the fibrous layer of mesenchymal
cells(neural crest) surrounding optic cup
• Starts at 7th week of gestation and is completed
by 5th month
39. Blue sclera
– Arrest in scleral
maturation
– Blue sclera, brittle
bones, and deafness
forms clinically
diagnostic triad of
osteogenesis imperfecta
Clinical Sig.
40. Development of epithelium
Surface Ectoderm
2 cell layers : Superficial layer
:Basal cell layer
Basal cells, wing cells, flattened cells
33
days
8
wks
26
wks
Cornea
41. Microvilli & Microplicae
• Remaining components of desmosomes
previously attached to desquamated cells
• Commence
ment of
surface cell
sloughing
• Protrusion
of
cytoplasm
• Consequent
developmen
t of microvilli
as a result
of
desmosome
reistance to
sloughing
42. Development of stroma
Secondary stroma
Secrete keratocytes that secrete type I collagen
fibers & matrix
Mesenchymal cells migrate into primary stroma
Primary stroma
Basal layer of epithelium cells secrete
collagen fibrils & GAGs
40
days
7th
wk
43. Development of Bowman’s layer
Condensation of superficial acellular part of
stroma
4 mnth and fully developed at birth
44. mesodermal cells extend beneath
the corneal epithelial cells
Primordial
endothelium
2 layered..1 rests
on the other(DM)
Development of endothelium
6th wk
45. Sclerocornea
Clinical Sig.
➢ Sclerization (opacification)of
peripheral or entire cornea
➢ Mesodermal dysgenesis
➢ Up to 4th mnth of fetal life,
cornea and sclera have
same radius
➢ Some factor arrests relative
decrease in corneal radius
of curvature during 4th or
5th month→Cornea Plana
47. Iris
The dilator muscle is not apparent until sixth
month, and differentiation of myoepithelial cells
continues after birth→pupillary miosis
Both layers of epithelium: marginal regions of optic
cup
Stroma and blood vessels - vascular mesenchyme
anterior to optic cup
Sphincter and dilator pupillae muscles -anterior
epithelium( only muscle derived from ectoderm)
48. Development of iris is a/w formation of anterior
portion of tunica vasculosa lentis.
The developing vessels extend into mesenchymal
cells that cover anterior lens surface and will
ultimately be incorporated into iris stroma
Towards end of gestation central iris stroma
(pupillary m/m) disappears forming pupil
The most anterior region of tunica vasculosa lentis
is replaced subsequently by pupillary m/m
Sometimes strands of this
tissue are left as
Persistent pupillary m/m
49. Anomalies of the iris
Corectopia
• Displacement of pupil
• Bilateral and symmetric
• A/w ectopia lentis, and the lens and pupil are
commonly dislocated in opposite directions
Polycoria
• More than one opening in the iris
• Result of local hypoplasia of iris stroma and
pigment epithelium
Clinical Sig.
50. Aniridia
– Partial or complete
absence of iris
– Iris tissue is usually
present, although it is
hypoplastic
Clinical Sig.
52. • Defective closure of
embryonic fissure
• usually inferonasal
Clinical Sig. Iris Coloboma
53. Anterior chamber
• Separation of corneal mesenchyme from lens results
formation of AC
• Mesenchyme anterior to slit→corneal endothelium
• Mesenchyme posterior to slit→primary pupillary m/m
• Iridocorneal Angle
➢ Loosely organised mesenchymal cell (neural crest)
occupies angle – trabecular meshwork (7th week)
54. Contd….
• 15th week – corneal endothelial cells extend to
angle recess /anterior surface of iris.
• 5th -7th month – angle is round.
• 3rd month - 4 years after birth-deepening of
anterior chamber due to differential growth rate of
adjacent tissues.
• End of 3rd month-small plexus of venous canaliculi
derived from mesodermal mesenchyme form
schlemm’s canal.
55. Contd…..
• 4th month – cells and their secreted extracellular
matrix form juxtacanalicular tissue.
• Beginning of 5th month-vacuolar configuration
appear in endothelial lining of schlemm’s canal
which marks the onset of aqueous humour
formation
56. Contd…
• Differential growth of vascular tunic results in
posterior movement of iris and ciliary body relative
to trabecular meshwork & exposure of outflow
pathways
• Corneal trabeculae enlarges & corneal
endothelium covering the angle recess regresses
If splitting & rebuilding of endothelial membrane
lining of early iridocorneal angle is arrested, a
block to normal outflow may result. Persistence of
endothelial (Barkan’s) membrane has been
postulated to be of significance in pathogenesis of
congenital glaucoma
57. Posterior chamber
• Develops as a split in the mesenchyme posterior
to developing iris and anterior to developing lens
• Anterior chamber and posterior chamber
communicate when pupillary membrane
disappears and pupil is formed.
58. Primary Lens Fibers
Lens
• Lens vesicle→ Single layer
• Cells of posterior wall of lens vesicle
➢ Formed upto 3rd month of gestation and are
preserved as compact core lens known as
embryonic nucleus.
Elongate rapidly Filled with
crystalline
Grow towards
anterior epithelium
obliterating the
cavity of lens
vesicle
59. Contd…..
• Secondary lens fibers – equatorial cells of anterior
epithelium which remain active throughout life
• Laid down concentrically
• Depending upon period of development ,named as:
➢ Fetal nucleus → 3-8 month, meet at sutures
➢ Infantile nucleus → last week of fetal life-puberty
➢ Adult nucleus → after puberty
➢ Cortex→ recently formed superficial lens fibers
62. Tunica Vasculosa Lentis
• Extensive capillary network,
spreading over posterior and
lateral surfaces of lens
• Arises from hyaloid artery
• Mesenchyme surrounding lens
• Encompasses lens : 9 wks
• Nourishment
63. Capillaries of tunica vasculosa lentis and anterior
pupillary membrane regress by 8th month
Anterior epicapsular remnants of vascular tunica gives
Persistent pupillay membrane
Iris strands may connect to anterior lens surface causing
Polar cataract
Small area of fibrosis on posterior capsule due to
incomplete regression of hyaloid artery where it attaches
to posterior capsule is seen as Mittendorf’s Dot
64. Capsule
• Basal lamina gradually thickens by deposition of
successive layers of basal lamina material to form
Lens Capsule
65. Lens Zonules
• Tertiary Vitrous in area of ciliary body folds
develop into lens zonules
• The ciliary epithelial cells then synthesize
collagen fibrils of zonular fibers.
• By 5th mnth of gestation, as they increase in
number, strength, &coarseness, fibers reach
the lens and merge with anterior & posterior
capsule
66. Anomalies of lens
Congenital aphakia
• PRIMARY:
-lens placode fails to develop from surface ectoderm
• SECONDARY:
-more common
-developing lens is spontaneously absorbed after
lens vesicle formation
Clinical Sig.
67. LENS COLOBOMA
Primary:
• Wedge shaped defect
or indentation of lens
in periphery
Secondary:
• Flattening or indentation
of lens periphery
caused by lack of ciliary
body or zonular
development
• Typically inferior and
may be a/w colobomas
of uvea
Clinical Sig.
69. Ciliary body
• Epithelium(both) develop from anterior part of the
2 layers of optic cup
• Stroma of ciliary body,ciliary muscles and blood
vessels :vascular layer of mesenchyme
surrounding optic cup
• At 4.5 months, Both pigmented & non-pigmented
epithelial cells show apical cilia that project into
intercellular space
• ↑ed prominence of Golgi complex & associated
vessels within ciliary epithelial cells
• These changes & presence of ciliary channels
betwn apical surface represent first production of
aquous humor
70.
71. Vitreous
Primary vitreous first appears at 5 wks & consists of
hyaloid vessels surrounded by mesenchymal cells,
collagenous fibrillar material & macrophages
Secondary vitreous is avascular and consists of type II
collagen fibrils and hyalocytes, (mesenchymal cells of
the primary vitreous) 8 wk
Primitive hyalocytes produce collagen fibrils that expand
volume of secondary vitreous
Continued development of secondary vitreous, until end
of 3rd month, is related to regression of hyaloid system &
simultaneous retraction of primary vitreous
72. • Persistence of primary vitreous & failure of posterior
tunica vasculosa lentis to regress result in persistent
hyperplastic vitreous (PHPV).
• Fibrovascular m/m , extends from ON along hyaloid
remnant and covers posterior capsule of lens
Toward end of 4th mnth of gestation,primary vitreous &
hyaloid vasculature atrophies to a clear, narrow central
zone, Cloquet’s canal
Clinical Sig.
At birth, Cloquet’s
canal persists as an optically clear zone emanating from
the
optic nerve to back of lens
73. • 3rd month, tertiary vitreous forms as thick
accumulation of collagen fibers between lens &
optic cup. These fibers are called marginal
bundle of Drualt
Drualt’s bundle has a strong
attachment to inner layer of optic
cup and is the precursor to
vitreous base & lens zonules.
74. Choroid
• Derived from inner vascular layer of mesenchyme that
surrounds optic cup
• 4th & 5th wk, choriocapillaris begins to differentiate
• Melanocytes of choroid originate from neural
crest(ectoderm)
• Melanocytes of iris (stroma): anterior portion of tunica
vasculosa lentis(mesodermal)
• Choroidal melanoma more common than iris melanoma
75. Anomalies of choroid
Choroidal coloboma
• Incomplete closure of
embryonic fissure
• Unilateral or bilateral.
Clinical Sig.
76. Retina
• Two walls of optic cup :
(a) Nervous retina : inner wall
(b) Pigment epithelium: outerwall
77.
78. Development of Macula
– Differentiation of neurons, photorecepters and glial
cells occurs early
– Different cell types established by 15th week.
– 24-26th week- thinning of ganglion cell & inner
nuclear layers - foveal pit -prominent in 7th month
– Only cones are present in fovea : taller and thinner
– 4th month: Remodelling /relocation of retinal layers
-continues till 4 years of age.
79. Optic nerve
-Develops in the framework of optic stalk as follows:
• Develops from nerve fibre layer of retina .
• Glial system of nerve –neuroectodermal cells
forming outer wall of the optic stalk.
• The glial septa surrounding the nerve bundles
are composed of astroglia that differentiate from
the cells of the inner wall of the optic stalk.
• Sheaths of optic nerve –formed from the layers
of mesenchyme like meninges of other parts of
CNS.
80. • At 6 wks, axons from developing ganglion cells
pass through vacuolated cells from inner wall of
optic stalk
• Emanating from center of primitive nerve is
hyaloid artery
• Glial sheath forms around hyaloid artery
• As hyaloid artery regresses, a space betwn hyaloid
artery & glial sheath enlarges.Glial cells in this area
migrate into ON and form primitive optic disc
• By 3rd month, optic nerve shifts nasally as
temporal aspect of posterior pole enlarges.
The tissue of Kuhnt, which circumferentially surrounds
intraocular part of ON & acts as barrier betwn ON and
retina, comes from glial tissue in the region of the disc
and mesenchyme from nearby developing retinal
vasculature.
81. Myelination
• Myelinization of optic nerve starts at chiasm at
about 7 months and progresses toward eye.
• Normally, myelinization stops at lamina cribrosa
at about 1 month after birth.
Myelinated nerve fibers occur if myelinization
continues past lamina cribrosa due to presence
of heterotopic oligodendrocytes or glial cells
within retinal nerve fiber layer.
82. Retinal vasculature
• Portion of hyaloid artery within optic stalk→CRA
• Hyaloid artery gradually atrophies & regresses
• Regession completes by 5th mnth
Remnant of hyaloid vasculature that doesn’t
regress: BERGMEISTER’S PAPILLA
83. • Regression of hyaloid vasculature stimulates retinal
vessel angiogenesis
• CRA grows from ON to periphery forming temporal
& nasal arcades
• Retinal arteries grow from ON towards ora serrata
& reach nasal periphery first (8 mnth)
• Even at birth, crescent of avascular retina present
in temporal periphery
The fact that a newborn infant has immature
temporal retina without complete vascularization
explains why there have been scattered cases of
retinopathy of prematurity in full-term infants.
85. ➢ Incomplete closure of
embryonic fissure
➢ Minor : Inferior crescent
➢ Fully developed :
typically present
inferonasally as a very
large whitish excavation
which looks like disc
Optic Disc Coloboma
Clinical Sig.
86. Optic disc drusen
• Intrapapillary refractile
bodies lying deep
beneath disc tissue
• Ophthalmoscope:
waxy pea like irregular
bodies
Optic disc pit
• Round or oval, gray or
white depression in the
optic disc
Clinical Sig.
87. ▪ Optic nerve head
appears abnormally
small due to a low no.
of axons
▪ Gray or pale disc
surrounded by light-
colored peripapillary
halo
▪ Double ring sign
Optic Disc Hypoplasia
Clinical Sig.
90. Lacrimal apparatus
• Lacrimal gland :from about 8 cuneiform epithelial
buds which grow by the end of 2nd month of fetal life
from the superolateral side of the conjunctival sac
• Lacrimal sac , NLD & Canaliculi
➢ From ectoderm of nasolacrimal furrow
➢ Gets buried to form solid cord, later canalized
-upper part→lacrimal Sac
-lower Part →NLD
➢ Some Ectodermal buds from medial margins of
eyelids canalise to form canaliculi
91. • Lacrimal gland (reflex) tear production does not
begin until 20 or more days after birth.
• Hence, newborn infants cry without tears
92. Anomalies of lacrimal apparatus
• Congenital Nasolacrimal Duct Obstruction
-Delayed canalization near valve of Hasner
-On pressure reflux of purulent material from punctum
• Congenital Dacryocele
-Distension of lacrimal sac by trapped amniotic fluid
-caused by imperforate valve of Hasner
Clinical Sig.
93. Extraocular muscles
▪ Derived insitu from mesenchymal tissue(mesodermal)
▪ Rectus and oblique muscles differentiate from
mesenchyme in region of developing eyeball
Appearing Sequence:
➢ LR,SR, LPS (5 wk)> SO,MR (6 wk) > IO,IR
▪ During development , get a/w axons of general
somatic efferent neurons of cranial nerve 3rd ,4thand
6th which innervate these muscles
94. Orbit
• Derived From :
➢ Mesenchyme Encircling Optic Vesicle( Above)
➢ Maxillary Process (Below & Laterally)
➢ Frontonasal Process(medially)
➢ Pre & Orbitosphenoid(behind)
➢ Membrane→3rd Mnth →Ossification
95. Periocular Tissues
• The frontonasal & maxillary processes of neural
crest cells occupy space that surrounds optic
cups by 4th wk.
• The bones, cartilage, fat & connective tissues of
the orbit develop from these cells.
• All bones of the orbit are membranous except
the sphenoid, which is initially cartilaginous.
• Ossification begins during 3rd mnth, & fusion
occurs between 6th & 7th mnth
96. Realignment of Globe
• Initially, axes of 2 optic cups & optic stalks form
an angle of 180°→decreases to 105°( 3 mnths)
• With continued enlargement remodeling; &
repositioning of head, face,& brain throughout
gestation, eyes become oriented in their anterior
position.
• At birth,axes form an angle of 71°
• Adult orientation of 68° is not achieved until age
of 3 years
97. To put in a nut shell
• Our cognitive capacity , behavioral
characteristics, physical appearance are
affected by our prenatal experiences & factors
such as maternal smoking, nutrition, stress, drug
use, diseases, etc.
• Attempts should be made to prevent these for
better reproductive outcome