1. Embryology of Eye
Varun Shrestha
First Year Resident
Nepal Eye Hospital
2013

2. Importance
• To understand the structure of normal adult
eye and its anatomic characteristics
• the pathogenesis of numerous congenital
anomalies of the eye that may occur as a
result of defective embryogenesis
• The various diseases of the eye

3. 3 elements have been identified that regulate:
• Growth Factors
 Fibroblast growth factors (FGF)
 Transforming Growth Factor- (TGF Insulin like Growth factor-I (IGF-I)
and TGF-
)
• Homeobox genes - DNA sequence found within genes that
are involved in the regulation of patterns of anatomical
development (morphogenesis)
 PAX 6
 HOX (HOX8.1, HOX 7.1)
• Neural crest cells

4. Synergistic action of these multiple trophic
factors appears to be a significant regulatory
tool for
• Initiating cellular activities and
• For limiting abnormal development

7.  Neural plate
Ectodermal cells of
anterior portion of
embryonic plate
proliferates + thickens
 Neural groove Medial
longitudinal furrow
 Neural fold Elevation
at 2 sides of the
neuroectoderm
 Neural Tube neural
folds meet at midline

8. At the anterior portion of the neural
tube 3 dilatations are formed

9. The eye begins to develop as a pair
of optic vesicles on each side of the
forebrain
Of the three germ layers of the embryo, only
two are involved in the development of eye
• Ectoderm – surface ectoderm
neuroectoderm
• Mesoderm

10. EMBRYOGENESIS OF EYE
• PRIMITIVE EYE  starts
in 3rd week of gestation
when anterior portion
of neural tube is
closing.
• It origins as optic pit
thickening on either
side of midline in the
ventrolateral region of
primitive forebrain

11. • The optic pit enlarges to
form 2 globular structures
at either side Primary
Optic Vesicles.
• Which connects to the
forebrain via a n Optic Stalk
• Primary optic vesicle meets
surface ectoderm

12.  During 4th week of gestation optical vesicle invaginates
distally and inferiorly  formation of two layered optic
cup
 Optic cup is widely open distally and inferiorly.
 Invagination also involves the optic stalk so this inferior
groove forms Optic fissure/ embryonic fissure

13. Invagination of optic vesicle
Rim of optic
cup
Lateral wall of
Forebrain
Embryonic fissure

14. Embryonic fissure
 Closes at 6th week
 Closure begins at centre and extends anteriorly and
posteriorly until only a small crescent remains open at
the posterior pole.
 IMPORTANCE: Through the fissure there is
 Outgrowth of axons from ganglion cells which form
the optic nerve
 Ingrowth of vascular elements which aids in
growth and development of the eye

15. Applied anatomy
• Failure of fusion of this fissure -6th/7th week
results in coloboma formation
Anterior extreme  Colobomas of iris
Posterior extreme  Colobomas of posterior
fundus and optic nerve
• Anterior and posterior aspects of cup are open
for longer time hence it is exposed longer
to teratogenic insults

16. Coloboma iris
Coloboma optic disc

17. RETINA
• Develop from two layers of optic cup
 Sensory retina is formed by the Inner layer of optic cup
 Retinal pigment epithelium is formed by the outer layer of
optic cup

18.  Retinal Pigment layer
It is a single layer of columnar cells
 initially it is non-pigmented but at 5th week melanogenesis
begins (Premelanosomesmelanosomes
Differentiation begins at posterior pole and proceeds
anteriorly
 Neurosensory layer
The anterior 1/5th  forms posterior surface of developing
ciliary body and iris
The posterior 4/5th  initially divided intoinner marginal zone -devoid of nuclei
outer primitive nuclear zone which has 9 rows
of nuclei

19.  Later the outer nuclear layer invades the inner
marginal layer at the time of closure of embryonic
fissure, so retinal Neurosensory cells divide into
 Outer neuroblastic layer which contains
horizontal, bipolar nerve cells, rod and cone cells
 Inner neuroblastic layer which contains
ganglion cells, amacrine cells, muller cells
 These layers are separated by the Transient nerve
fiber layer of Chievitz which later forms the inner
plexiform layer
 The inner 9 layers of retina are formed by merging of these two
cell layers
 By the 8th month of fetal life all layers of retina are recognizable

20. • Ganglionic cells are the
first cell of retina to be
clearly differentiated
• Cones outer segment
form - month
• Outer Rods segment form
-7 month
• photoreceptor cells
continue to form after
birth so it develops the
ability for increasing
resolution and sensitivity

21. • Ora serrata – is a wavy line that lies between the small non
nervous layer near the edge of cup large photosensitive
portion in the inner layer of optic cup
• Macula – has localized increase of superimposed nuclei in the
ganglion cell layer, lateral to optic disc, in mid term
• Fovea centralis – during 7th month, thinning of centre of
macula due to peripheral displacement of ganglionic cells.
Ganglionic layer
Inner Nuclear layer
Foveal Depression
Outer plexiform layer/Henle’s
layer *

22. Applied Anatomy
 Areas where RPE does not form(sometimes along
the line of closure) the underlying
choroid/sclera/neuroretina is hypoplastic.
 Retinal detachment- Potential space between the
inner and outer layers of optic cup is the site for
retinal detachment.
 Foveal region is extremely thin, devoid of ganglion
cells and retains relative transparancy, allowing
persistent transmission of underlying highly
vascular choroidal hue eg. Cherry Red spot
(Sphingolipidoses)
 Juvenile Retinoschisis- splitting of the retina in the
nerve fiber layer.

23. OPTIC NERVE
 Optic stalk and optic axons together form the optic nerve.
 Its the constricted elongated area between primitive eye
and forebrain
 Initially there is an inner zone (neuroectodermal cells) and
outer zone (undifferentiated neural crest)
 th weeksome cells of inner region vacuolate+
degenerate+ remaining inner zone differentiates into glial
cells.
 Axons from ganglion cells run through the inner layer of
stalk
 Cells of inner layer encroach on the cavity of the stalk 
cavity disappears
 End of gestation Development of lamina cribrosa

24.  Myelination of axons of optic nerve begins just before birth and
continues some time after birth
 Optic disc- the point where the axons from ganglionic layer
of retina converge to leave the posterior surface of optic cup
along with the optic stalk
 Optic chiasma- partial decussation of the axons of the 2
optic nerve
 Optic tracts
 Lateral geniculate bodies
 Tectum of midbrain

26. • Applied anatomy:
• Optic nerve
– Aplasia
– Hypoplasia
• Morning Glory
Syndrome - central
excavation surrounded by an
elevated rim of pink neuroglial
tissue with the vessels
emerging radially from the disc
as spokes in all directions
• Pit of the optic disc

27. Lens
• Begins development at 3rd week
• Derived from surface ectoderm
• Triggered by interaction of forward growth of optic
vesicle with surface ectoderm thickens and forms
lens placode
• It invaginates to form lens pit that eventually
seperates + meets at the margin lens vesicle

28. CORNEAL
EPITHELIUM
ANTERIOR WALL- single layer of
cuboidal epithelium
POSTERIOR WALL- increases in
length and form elongated
fibres that projects into lumen
of vesicle (crystallin)
NUCLEAR BOW- nuclei of the
lens fibers move anteriorly to
form a convex line

29. • Nuclei disappears.
• Additional lens fibers are formed by mitotic
division of the anterior epithelial cells at preequatorial region Secondary fibers
• These are formed through out life.
• Basal ends are attached to the basal lamina
while apical ends extends to primary fibers
As the fibers are laid down concentrically
laminar appearance of the lens
• New fibres are added concentrically around the
old central fibres around the equator

30. • Drawing shows
formation of the
lens vesicle and
optic cup. The optic
fissure is present
because the optic
cup is not fused
inferiorly.

31. Different layers seen in adult eye:
• Embryonic nucleus- 1st to 3rd month of embryonic life
(Primary fibers)
• Fetal nucleus- 3rd to 8th month of fetal life
• Infantile nucleus- last weeks of fetal life to puberty
• Adult nucleus- formed after puberty
• Cortex- recently formed fibers, beneath epithelium
anteriorly, beneath capsule posteriorly

32. • SUTURES  The linear juncture where the fibers terminate
and abut each other.
• Y Sutures- begin to form  2nd month
 Anterior upright
 Posterior inverted

33. • Later in gestation and following birth
sutures become complex and
dendriform.
• LENS CAPSULE
 Vascular lens capsule formed from
mesenchyme surrounding the lens,
Disappears after birth
 True lens capsule formed from
Thickened basal lamina, which
develops from lens epithelium.

34. • The Zonular Apparatus begins to develop after
the tertiary vitreous has formed.
• Ciliary Epithelial cells synthesize collagen
fibrils of the zonular fibers.
• By 5th monthincrease in number, strength
and merge with the anterior and posterior
capsule.

35. Applied Anatomy
 Unequal growth of fibers from posterior wall + New fibers growing
from equatorial regions  Elliptical shape of lens
 Lens epithelial cells left behind in the capsular bag after ECCE 
PCO (posterior capsular opacification) development.
Clinically 2 types of PCO,
fibrosis type proliferation and migration of lens epithelial
cells, which undergo Epithelial-to-Mesenchymal Transition
fibrous metaplasia producing folds and wrinkles in the
posterior capsule.
pearl typeremnants located at the equatorial lens region
(lens bow) causes regeneration of crystallin expressing
lenticular fibers and forms Elschnig pearls and Soemmering
ring
 If sutures are not formed and the fibers meet at a single point at
anterior and posterior pole a pit would be formed poor optical
properties

36. CONGENITAL CATARACTS

37. THE VITREOUS BODY
Develops between the lens and optic cup
• Primary vitreous– formation at 1st month
Network of delicate cytoplasmic processes
derived partly from lens and partly from
retinal layer of optic cup and mesenchymal cells
Supplied by hyaloid vessels and its branches
• Secondary vitreous - formation at 2nd month
Between primary vitreous and retina and is avascular
Derived from retina and replaces the primary vitreous
extracellular matrix composed of type II collagen+
hyaloctes
Hyaloid vessels undergo atrophy – hyaloid canal (5th -6th
mth-) cloquet’s canal which extends from optic nerve
head and posterior surface of lens, Funnel shaped

38. • Tertiary vitreous- at 4th month
• Between ciliary processes and lens capsule
• Large no. of collagen fibres develop with formation of zonular
fibres

39. • Applied anatomy
• Mittendorf’s dot: remnants of anterior end of
hyaloid artery associated with posterior polar
cataract & attached to posterior lens capsule.
• Subluxation/Ectopia lentis: Partial or total failure
in Tertiary vitreous development
• Bergmelster’s Papillae: flakes of glial tissue
projecting from the optic disc
• Persistent Primary hyperplastic vitreous: U/L,
premature child.

40. UVEA
•
•
•
•
Middle vascular layer of eyeball
Composed of iris, ciliary body choroid
Stroma of all these are mesodermally derived
Consists of blood vessels, pigmented cells called
melanocytes and connective tissue.

41. IRIS
 Developed from 2 layers
 Mesoderm – Anterior stroma
 Neuroectoderm-
 iris pigment epithelium
 sphincter and dilator muscles
 pupillary membrane is formed by condensation of
mesenchyme situated in the anterior surface of the lens
 2 layers of neuroectoderm forming the edge of optic cup
extend to the posterior surface of pupillary membranethese structures fuse to become iris
 Opening in the central part of iris becomes the pupil
 Pupillary membrane begins to degenerate at about 8th
months of gestation

42.  Applied anatomy
 Varying amount of atrophy of stromal vessels (pupillary
membrane) while peripheral membrane remains well
developed produce the fine architecture of iris crypts
 Pigmentation of stroma doesn’t become evident until
after birth, hence newborns usually have blue iris

43. Polycoria, Ectopia, Corectopia, Aniridia

44. CILIARY BODY AND SUSPENSORY LIGAMENTS OF LENS
 Mesenchyme at edge of optic cup forms the Connective tissue of ciliary body,
 Smooth muscle fibres of ciliary muscle,
 suspensory ligaments of lens
 2 epithelial layers formed from neuroectoderm at the
edge of optic cup
 outer pigmented
 Inner devoid of pigment
 Ciliary body is situated between future iris epithelium and
peripheral retina
 Ciliary epithelium undergoes folding to form 70-75 ciliary
processes

45.  CHOROID
Middle vascular coat of eyeball. Begins to form at the
anterior region of the cup & proceeds posteriorly.
Formed from mesenchyme surrounding the optic
vesicle
Has layers. The innermost Bruch’s membrane is
derived from basement membrane of RPE
, choriocapillaries layer, Elastic tissue and collagen
fibrils
The outer
layers
layers are the - vascular and capillary
During 5th month melanocytes of neural crest origin
may be seen
Melanocytes of neural crest origin are predisposed to
development of malignant melanoma

46. NUTSHELL:
 Iris muscle-ectodermal in origin
 Ciliary muscle is mesodermal in origin

47. CORNEA
Formation of cornea is induced by lens and optic vesicle
formation
 Epithelium derived from – surface ectoderm
 Bowman’s membrane and Substantia propria – mesenchyme
 Descemet’s membrane – endothelial cells
 Endothelium – neural crest

48. Keratoconus
• Is a condition when the
cornea assumes a
conical shape secondary
to stromal thinning

49. SCLERA
 Outer tough fibrous coat of eyeball
 Originates as the condensation of mesenchyme outside
the optic cup  7th week of gestation
 First forms at the limbal region and progresses
peripherally until posterior pole is reached 5th month
 Primitive mesoderm differentiates into collagen and
elastic fibres of an adult sclera

50. ANOMALIES
MICROCORNEA
• Adult cornea<10mm in
horizontal diameter
• Related to fetal arrest of
growth of cornea in 5th month
MEGALOCORNEA
• diameter 12mm or > at
birth&13mm or>after 2 yrs
• Due to failure of optic cup to
grow &of its anterior tips to
close

51. Sclerocornea
• There is ‘sclera-like’
clouding of cornea
• Disorder of second wave
mesenchyme migration
• 90% bilateral

52. ANTERIOR CHAMBER
 It arises as a slit in the mesenchyme between the
surface ectoderm and developing Iris.
 th week angle of the anterior chamber is
occupied by mesenchymal cells of neural crest
originTrabecular meshwork
 rd monthSchlemm’s canal develops from small
plexus of venous canaliculi. The endothelial lining of
Schlemm's canal is mesodermal in origin.
 th monthVacuolation of the endothelium around
Schlemm's canal occurs individual cells are
connected by zonulae adherentes
 Final differentiation of definitive filtration apparatus
occurs shortly before birth.

53. Schlemm canal
Trabecular
meshwork
Scleral spur

54. POSTERIOR CHAMBER
• Split in the mesenchyme posterior to the
developing iris and anterior to the developing
lens.
• Anterior and Posterior Chamber
communicates when the pupillary membrane
disappears and pupil is formed
• Aqueous humor fills these two chambers

55. VASCULATURE
• At 5-6mm stage
simple endothelial tubes bud from internal
carotid artery
grow towards developing optic cup
• 2 Main vessels in this period
 dorsal ophthalmic artery
 ventral ophthalmic artery
Invests the more medial portion
of the cup & almost disappears
except a portion of Long
Posterior nasal ciliary
artery(LPNCA)
At 3rd week branches to form hyaloid artery
which enters the embryonic fissure at 7-8mm
stage
Becomes definative dorsal opthalmic artery at
th week
Supplies the TLPCA, SPCA,CRA
• The system drains into future cavernous sinuses by way of
plexuses

56. HYALOID VASCULAR SYSTEM
Embryonic intraocular vasculature system is divided into 2
component
 Anterior system
 In the region of iris
 Composed of pupillary membrane
 Posterior retrolental system
 within vitreous
 composed of



hyaloid artery
vasa hyaloidea propria
tunica vasculosa lentis

57. ANTERIOR SYSTEM
 MAJOR ARTERIAL CIRCLE OF IRIS:
anastomosis of the anterior ciliary
arteries with the Long posterior
ciliary arteries, near the root of
the iris
 PUPILLARY MEMBRANE: Radial
vascular loops over the surface of
the iris and lens+ formed by
Annular vessel & major arterial
circle.
 MINOR ARTERIAL CIRCLE OF IRIS:
Central portion of the pupillary
arcades disappear but the
peripheral remains as minor
arcade.

58. Applied Anatomy
• Persistent pupillary
membrane

59. POSTERIOR SYSTEM
 HYALOID ARTERY
 Branches from the Dorsal ophthalmic artery- 3rd
week- enters the optic cup via embryonic fissure
 Grows anteriorly towards lens.
 Supplies lens, vitreous and developing optic nerve.
 By 4th month many branches bud off to form main
branches of central retinal artery- the first
permanent intraocular blood supply.
 Continues to be an important source of nutrition till
the beginning of 8th month of gestation.

60.  VASA HYALOIDA PROPRIA
 Small capillary branches that extend from
main trunk of hyaloid artery through out
vitreous
 Anastomose with each others and with
tunica vasculosa lentis

61.  TUNICA VASCULOSA LENTIS
 Formed by terminal branches of main trunk of
hyaloid artery
 2 branches

Anterior tunica vasculosa lentis
 Posterior tunica vasculosa lentis
 Extend around equator of lens to form lateral
tunica vasculosa lentis/ capsulopupillary vessels
 Anastomose with anterior tunica vasculosa
lentis and makes a drainage system through
annular vessels and later in gestation through
ciliary vessels

62. Long Posterior ciliary
arteries
Anterior vascular
capsule
capsulopupillary
portion
Posterior vascular
capsule
Hyaloid Artery
Tunica
Vasculosa
Lentis

64. HYALOID VASCULAR SYSTEM(cont..)
• Begins regressing even before some
of its components have not reached
peak of development
• Stimulus – unknown
• 1st to regress
 vasa hyaloida propria
 tunica vasculosa lentis
Finally main hyaloid artery

65. RETINAL CIRCULATION
• By 7th -8th month of gestation, retinal vessels would have
extended nasally to ora serrata but only to equator temporally
• Vessels reach ora on temporal region only close to term and
even after birth
• APPLIED ANATOMY: Retinopathy of prematurityexcessive
O2 in premature infantsvasoconstrictionobliterated
veinsneovascularizationvascular area is nonstretchable (detaches)/ non-vascular area is stretchable.

66. UVEAL CIRCULATION
 Develops from vasoformative paraxial mesoderm that surrounds
the optic cup
 6th wk-
 Common temporal ciliary artery branch of dorsal
ophthalmic artery runs along the temporal aspect of
stalk & cup
 Common Nasal ciliary artery branches of ventral
ophthalmic artery runs along the nasal aspect of stalk
& cup
 These two vessels are the precursors of long
posterior ciliary artery
 These anastomose with each other posteriorly &
anteriorly to form greater circle of iris

67. •
3rd
month
12 -15 short posterior ciliary arteries develop
from dorsal ophthalmic artery
Anterior ciliary artery
Develops from small tributaries from muscular &
lacrimal branch of ophthalmic artery
Anastomose with branches of long posterior
ciliary artery

68.  Develop as folds of surface
ectoderm above and
below the developing
cornea.
 Folds fuse at 3rd month
intrauterine life.
 A closed
space, conjunctival
sac, exists in front of
cornea.
 Separation of eyelids starts
by 5 month and completes
by the 7th month.
EYELIDS

69.  Connective tissue and tarsal plates Mesenchymal core
of the lids
 Eyelashes epithelial buds from surface ectoderm
 First appear in upper lid
Arranged in 2-3 rows
 Glands of Zeis and Moll ciliary follicles
 Tarsal/Meibomian glands develop as columns of
ectodermal cells from lid margins
Gland of Zeis and Moll
Mebomian gland
Orbicularis Oculi
Cornea

70. APPLIED ANATOMY- EYELID
• cryptophthalmos Failure of separation of
eyelids –
In cases of cryptophthalmos usually cornea is
absent
• Ankyloblepharon adhesion of eyelids
• Epicanthal Foldspalpebralis, tarsalis,
supraciliary and inversus

71. EXTRAOCULAR MUSCLES
• From the mesenchyme in the region of
developing eyeball –
four recti muscles
superior and inferior oblique muscles
• Initially represented as a single mass of
mesenchyme
• Later separates into distinct muscles, first at
insertions and later at their origins

72. • Levator palpabrae superioris formed last
splitting from the mesenchyme that forms the
superior rectus
• During development, muscles become
associated with IIIrd, IVth and VIth cranial
nerves
• Orbicularis oculi muscle• Mesenchyme of 2nd pharyngeal arch
• Invades eyelids
• Supplied by VIIth cranial nerve

73. APPLIED ANATOMY OF EOM

During congenital ptosis there is paralysis of superior rectus
muscle .

74. LACRIMAL GLAND
 Form as series of epithelial
buds, which grow
superolaterally from superior
fornix of conjunctiva into the
underlying mesenchyme
 Buds canalize- secretary units
multiple ducts
 With the development of
Levator palpabrae superioris,
gland divides into orbital part
 palpebral part
 No tear production until third
month after birth

75. LACRIMAL SAC AND NASOLACRIMAL
DUCT
• Develop as solid cord of ectodermal cells
between the nasal process and maxillary process
of the developing face
• The cord later canalizes – nasolacrimal duct
• Superior end dilates to form lacrimal sac
• Further cellular proliferation forms lacrimal ducts
which enters each eyelid

76. APPLIED ANATOMY

At junction of advancing cords there is a membranous plate,
and it is at this site that block of NLD usually occurs in
congenital NLD block

Incomplete canalization watering from eyeinfection of
the lacrimal duct and sac

77. ORBIT
 Orbital bones  mesenchyme that encircles the
optic vesicle
 Medial wall – lateral nasal process
 Lateral and inferior wall- maxillary process
 Superior wall- mesenchymal capsule of
forebrain
 Posteriorly – from bones of base of skull
 Orbital bones form in membrane, except those
forming the posterior part which form in
cartilage

78. • Axis of orbitAt 1st month- 180 degrees laterally
 At 2nd month - this angle begins to lessen
 At 3rd month 72 degrees
 Later stabilises at 45 degrees
• Development of eyeball is at faster rate than
of orbit; at 6th intrauterine life anterior half of
eyeball projects beyond orbital opening

79. Primordial tissues and its derivatives
• Neuroectoderm
• Surface ectoderm
• Mesoderm

81. SUMMARY OF OCULAR
EMBRYOGENESIS
rd week
• Optic groove
appears
th week
• Optic pit
develops into
opticvesicle
• Lens plate forms
• Embryonic
Fissure develops
st month
• Lens pit then
Lens vesicle
form
• Hyaloid vessels
develop

82. ½ month
• Closure of
embryonic fissure
• Proliferation of
neural retinal cells
• Appearance of
eyelid folds and
nasolacrimal duct
th week
• Formation of
embryonic nucleus
of the lens
• Sclera begins to
form
• Migration of waves
of neural crest
• First wave: formation
of corneal and
trabecular
endothelium
• Second wave:
formation of corneal
stroma
• Third wave:
formation of Iris
stroma

83. rd month
• Differentiation of precursors of Rods
and Cones
• Anterior Chamber appears
• Fetal nucleus starts to develop
• Sclera condenses
• Eyelid folds lengthen and fuse
th month
• Formation of Retinal vasculature
begins
• Hyaloid vessels begin to regress
• Formation of physiological optic dsc
and Lamina Cribosa
• Canal of Schlemn appears
• Bowman’s membrane develop
• Formation of major arterial circle and
spinchter muscle of Iris

84. th month
• Photoreceptors
differentiate
• Eyelid separation
begins
th month
• Differentiation of
dilator pupillae
muscle
• Nasolacrimal system
becomes patent
• Cones differentiate
th month
• Rods differentiate
• Myelination of optic
nerve begins
• Posterior movement
of anterior chamber
angle
• Retinal vessles start
reaching nasal
periphery

85. th month
• Completion of
anterior
chamber angle
formation
• hyaloid vessels
disappear
th month
• Retinal vessels
reach temporal
periphery
• Pupillary
membrane
disappears
After birth
• Macular region
of the retina
develops further

86. REFERENCES
 Peyman, Gholam A., Sanders and Goldberg,
Principles and practice of
Opthalmology(Vol.1),1st Edition,Jaypee:Delhi7,1987
 Snell, Richard s. and Michael A. lemp, Clinical
anatomy of the eye,2nd Edition, India:Blackwell
science,1998.
 Ramanjit Sihota, Radhika Tandon, Parson’s
diseases of Eye- st Edition, Elsevier 2011
 T.W. Sadler, Langman’s Medical Embryology, 9th
Edition
 Internet Resources