Try to visualise the development of the eye as you read.

Also draw many diagrams as you

read.

This just a reminder.

The aim of my course is to prepare you for the ICO Assessment and help you pass at your first attempt.

Pass rate among my students is the highest in the world. If you work hard you will pass at your first attempt.

There is only one short cut to pass this Assessment:

Intelligent hard work

The lessons are based strictly on the syllabus.

It starts from the beginning of the ICO syllabus.

Please read every lesson very thoroughly.

Then read the topic in the books with you. Make notes of all the important facts that are not found in my lessons.

Please send them to me and I shall incorporate them in the lessons.

Then prepare as many MCQs as possible after each topic.

Preparation of MCQ will make you

think
help you to recollect what you have studied
make you realise your weak areas
help you to remember what you have studied.

Slave to prepare the MCQs so that you will become a master of MCQs.
The future trend of the Final FRCSEd is also moving towards MCQs. Your training here will be useful to you till you pass
your final Fellowship examinations.

The MCQs must be prepared separately in Microsoft WORD, and spell checked.
It must have an heading like this:
Orbit MCQs prepared by ……
Each MCQ must have 5 subdivisions abcde.
It must be marked (T) of (F) after each subdivision.

Answer the MCQS and keep it with you.

The correct answers will be sent with the next lesson. Then, you can assess your performance.

You will have the access to the next lesson ONLY after I receive your
MCQs.

ASSIGNMENTS AND MCQs ON EMBRYOLOGY (Ocular development)

1)Chronological sequence of events in the formation of the eye.

Developmentally and functionally the eye is an extension of the central nervous system.
Eye develops from surface ectoderm, neural ectoderm, neural crest, and mesodermal
mesenchyme. The development of the eye starts around the 22nd day. It is essential to
know the development of the embryo in first 21 days.

Development of embryo.

Events of first 3 weeks. [21 days]

First week. [7 days]

The male and female gametes unite at fertilization within the oviduct. It is diploid cell,
called zygote. This zygote undergoes cleavage as it travels towards the uterus. In 30-cell
stage [morula] the cavity appears in the zygote [blastocyst cavity.]. At this stage a
peripheral outer cell mass [trophoblast] and inner cell mass [embryblast] are formed.
The embryoblast is heterogeneous collection of cell
Ls and it leads embryo proper. The trophoblast differentiates into syncytio and
cytotrophoblast, which contributes to the development of fetal component of the placenta.
By day 5 or 6, the embryo is a hollow spheroid of around 100 cells [blastocyst]. Around
this day the blastocyst commences implanting to the endometrial lining of the uterus.

2nd week. [From 8th day]

Two cavities appear in the embryo proper [embryoblast]. The [1.] amniotic cavity is lined
by the epiblast cells, and the [2.] yolk stalk lined by the cells of hypoblast. There is
double layer formation at the impinge of these two layers, called primary ectoderm
[epiblast] and primary endoderm [hypoblast]. At this stage it is a bilaminar disc. This
leads to proper embryo.

3rd week. [From 15th day]

At the caudal end of the primitive ectoderm [epiblast], there is a formation of primitive
streak or primitive knot. From here the primary ectodermal cells detach and migrate
laterally and cranially into the space between ectoderm and endoderm to form third germ
layer [intraembryonic mesoderm] and some cells replace the original hypoblast to form
the definitive or secondary hypoblast. Formation of the primitive streak establishes the
craniocaudal axis and bilateral symmetry of the future embryo.
The formation of the notochord on the primitive streak induces the formation of the
neural plate. By the paraxial mesodermal condensations [somites] along the neural plates,
the neural tube is formed. The neural tube is the precursor of the central nervous system.
A special cells, [neural crest cells] detach from the margins of the neural folds and
undergoes extensive migration.
At 22nd day, the embryo is 2-mm length with eight pairs of somites.
Development of eye and other from 22nd day as follows,

Day. 22nd. [2 – 3 mm]

 Optic sulci.
 Neural crest.
 Surface ectoderm.
 Mesoderm/somitomeres.

Day. 27th [4-5mm].

 Optic vesicle.
 Neural crest cells steaming over the optic cup and stalk.
 Lens placode.
 Retinal disc.
 Cavity of the optic vesicle.
 Optic stalk with cavity.
 Pharyngeal arches and clefts.
 Heart bulge.
 Umbilical cord.

Day 29. [6-7mm]

 Condensed mesenchyme around the optic cup.
 Optic cup rim.
 Lens vesicle.
  Lens pit.
 Hyaloid vessels.
 Maxillary swelling.
 Mandibular swelling.
 Nasal and frontal prominences.
 Limb buds.
Day. 37th [8-11mm]
 Future corneal epithelium.
 Primary lens fibers.
 Future neural retina.
 Future RPE
 Future subretinal space.
 Ear swellings.
Day 44. [13-17mm]
 Lids forming.
 Future corneal endothelium and stroma.
 Tunica vasculosa lentis.
 Hyaloid artery.
 Developing sclera.
 Developing choroid.
Day 50th [20-30mm]
 Conjuctival sac.
 Lid fusion.
 Anterior chamber.
 Cornea
 Vitreous
 Ganglion cells in optic nerve
 Ganglion cells.
 Optic nerve sheaths.

Chronological sequence in the formation of embryonic eye

from 2 weeks to 16weeks (4 months)

embryonic tissues involved:

1. surface ectoderm lens plate lens vesicle lens, corneal epithelium

and endothelium, conjunctiva and skin of eyelids, lacrimal and accessory glands,
drainage system, vitreous also partly formed by mesoderm.

2. neural ectoderm bud optic stalk & optic vesicle

simultaneous invagination of optic stalk and optic vesicle
optic stalk choroidal fissure its fusion choroidal tube for hyaloid artery

and after 16 weeks for central retinal artery and vein

 optic vesicle optic cup approximation of inner and outer cell walls

outer wall of optic cup becomes a single layer pigmented epithelium of

retina, epithelium of the ciliary processes, iris and sphincter and dilator pupillae

inner wall of optic cup undergoes differentiation to form 1. the

outermost layer, rods and cones, 2. the inner layer of bipolar cells
and 3. innermost layer of ganglion cells, and their respective nerve fibres.
Macular development is not complete until 6 months after birth.

3. mesoderm forms sclera

ii stroma of cornea, conjunctiva, iris, ciliary body,
iii extraocular muscles, eyelids, hyaloid artery, sheaths of optic nerve
iv choroid
v connective tissue
vi blood supply of eye
vii bony orbit
viii vitreous
ix anterior chamber

4. endoderm does not contribute to the formation of the eye

Development of the eye takes place at the anterior end of the neural tube. The optic
vesicle is attached by optic stalk on either side to the forebrain. The neural tube lies in
the mesoderm.

2.5mm or 2 week stage : neural groove

4 mm or 3 week stage : fusion of neural groove, separation from surface ectoderm,

budding of neural ectoderm to form the optic stalk and optic vesicle. Thickening of the
surface ectoderm to form the lens plate opposite the optic vesicle. Simultaneous
invagination of optic stalk and optic vesicle to become choroidal fissure and optic cup
respectively.

9 mm or 4 week stage : lens plate separates from the surface ectoderm to form lens
vesicle
to lie free in the rim of the optic cup. Mesoderm forms a network of capillaries encircling
the optic cup to become the choroid by 6 weeks.

10 mm or 5 week stage : pigmentation of the outer wall cells of the optic cup to form a
single layer of pigment epithelium and Bruch’s membrane
differentiation of the inner wall cells into 3 other types of functional cells and their
respective nerve fibres of the retina.

13 mm or 6 week stage : choroidal fissure closed. Posterior lens cells grow forward.
Eyelid
develops from mesoderm except its skin and conjunctiva.

26 mm or 7 week stage : the axons of the ganglion cells of the retina form the optic
nerve. Mesoderm between the lens and the surface ectoderm forms the anterior
chamber, Schlemn’s cannal, trabecular meshwork and vascular septa of the optic nerve.

50 mm or 12 week stage : the rim of the optic cup forms the epithelial lining of the iris,
ciliary body and ciliary processes. Mesoderm infiltrates into these structures to form the
stroma. Neural ectoderm forms sphincter and dilator pupillae.

100 mm or 16 weeks : general structure of eye formed

Further development consists of differentiation, more rapidly in the posterior than in
anterior segment in early gestation and then reverses later.

2)Neuroectoderm differentiation.

Since eye is an extension of the central nervous system, a few considerations of the
development of the central nervous system are considered here.
Neural ectoderm give rise to
 Retina and retinal pigment epithelium.
 Sphincter and dilator pupillae
 Posterior pigment epithelium of the iris
 The neural portion of the optic nerve and chiasma.
The ectoderm on the dorsal surface of the embryo forms a thickness in the mid-region to
form the neural or medullary plate. These cells are called as the neural ectoderm. By 18
days a central depression developed in the neural plate [neural groove] and lateral plates
[neural folds]. The two walls fuse to form the neural tube. The fusion begins in the mid-
region and progress both anteriorly and posteriorly. Before the closure of the neural tube
at the anterior end, the same neural folds develops small lateral grooves [optic sulcus] to
represent future eyes at the anterior end of the embryo. This optic sulcus enlarges to form
the optic invaginations to become the optic vesicles. These optic vesicles are in contact
with the surface ectoderm externally.
In the region of the future neural folds, the neuroectodermal cells proliferate to produce a
population of neural crest cells. These cells play an important role in the development of
the eye. Most of the neural crest cells migrate away from the neural tube to differentiates
many body structures including cephalic cartilages, bones and ligaments, leptomeininges,
dental papillae, schwann cells, peripheral sensory and autonomic nerves, ganglia or
cranial nerves 5, 7 9 and 10, spinal ganglia, dermis and melanophores of the skin and
many cells of the endocrine system. The cells that remain attached to the neural plate
differentiate into the cerebral and spinal ganglia and the roots of the dorsal nerves.

Development of optic vesicle.

Is a hollow, symmetrical, hemispherical outgrowth on the lateral wall of the forebrain
vesicle. It is lined by high columnar with nuclei arranged in several layers. The cells of
the inner surface are ciliated. The outer surface of the cells is covered by a thin basal
lamina. It is connected to the lower region by the optic stalk. These vesicles are separated
by the frontonasal process. In 19-mm embryo, the direction of growth makes an angle of
65 with the midsagittal plane, where as in the adult the corresponding angle made by the
optic nerve is 40 degrees.
By 28 days [embryo 7.6-7.8], invagination of the optic vesicle and optic stalk takes place.
In the process of invagination, differential growth and movement of the cells causes the
temporal and lower walls to move inward against the upper and posterior walls.
The cavity of the optic vesicle or optic ventricle [future subretinal space] is continuous
via the lumen in the optic stalk. This communicates with the future third ventricle.
By the end of the embryonic period [week 8] the optic vesicle leads to the formation of
the thin layer [future retinal pigment epithelium] and thicker inner layer [future inner
retina]. The optic vesicle is formed by a lateral out-pouching from the diencephalon and
is fully formed by day 25. The proximal portion of the optic vesicle becomes constricted
to form the optic stalk and the dilated distal segment forms the optic cup, both become
involuted during the fifth week producing a groove on their inferior aspects [known as
the optic or choroidal fissure]. The hyaloid artery and surrounding vascular mesenchyme
are enclosed in the optic fissure. The optic cup closes in the fifth week, followed by
closure of the optic stalk that proceeds from the forebrain towards the cup in week six.
The optic vesicle consist of an outer and inner layer. The outer layer is composed of
pseudostratified columnar cells with pigment granules being present as early as the third
week of gestation, this layer will form the retinal pigment epithelium. The inner layer
[which will form the neural retina] consist of an outer nuclear and inner marginal zone.
Mitosis is maximum in the outer zone of inner layer and is completed by 15 weeks,
whereas the cells of future retinal pigment epithelium continue to divide late into fetal
life. As mitosis finishes differentiation begins, this is initiated in the marginal zone. The
cilia found in the outer nucler zone of inner layer disappears by the seventh week.
By 7 week of gestation the neural epithelium has separated into inner and outer
neuroblastic layers. The inner layer will produce ganglion and amacrine cells whereas the
outer layer gives rise to horizontal and bipolar elements. Lamination is essentially
complete by 4 ½ months and the oraserrata by 6 months. Photoreceptors are thought to be
derived from cilia found in the outer nuclear zone.
 The optic vesicle is surrounded by the Mesenchymal cells except at the apex of
the vesicle, which is closely opposed to the surface ectoderm.
 Lens placode formation coincides with formation of a constriction in the optic
vesicle at its attachment to the wall of the forebrain to form the optic stalk.
 The active growth of the optic cup is not uniform around the circumference.
 By 29 day the invagination of the retinal disc complete.
Optic stalk. [Embryonic, fetal, choroidal or optic fissure]
It is surrounded by a basal lamina. The margin of the fissure comprises the inner neural
retina [consists of several layers] and single layer of retinal pigment epithelium. In the
early stage of fusion the outer layer of the cup become inverted into the fissure. The
longitudinal groove of the optic stalk which extends into the optic stalk, acts as a
temporary deficiency in the cup through which vascular mesenchyme and a branch of the
ophthalmic artery, becomes incorporated into the fissure and thus gain access to the
growing lentoretinal space. The fusion of the optic stalk commences at the midportion of
the optic stalk and continuous both proximally and distally. By the end of sixth week the
growing edges of the choroidal fissure meet and fuse with hyaloid vessels and associated
mesenchyme in the center. Distally the fused margins form the pupil and proximally it
forms the entry point for the central retinal artery and vein.
Congenital malformations of optic vesicle and fissure.
Coloboma.
 As the result of a failure of closure of the inferio- nasal optic fissure fusion.
Coloboma of iris.
 Inferior nasal defect in stroma, smooth muscle and pigment epithelium.
Ciliary body Coloboma.
 Absence of ciliary process.
 Presence of diminutive muscle
 Adjacent lens indented.
 Failure of formation of Zonular fibers.
Coloboma of Retina.
 In adjacent retina proliferation of neuroblastoic tissue leads to the formation of
rosettes.
 Absence of Bruch membrane and choroidal tissue.
 Underlying sclera normal.
 Glial and vascular ingrowth from the retina across the bed of Coloboma.

Development of the Retina.

At 26 days of gestation [4mm] the inner layer of the optic vesicle undergoes mitosis to
form 3 or 4 layers of compact cells. By 32-33 days the retina consist of 5 or 6 layers of
neuroepithelial cells. This is divided into inner 1/3rd and outer 2/3rd. The inner layer [inner
marginal layer] faces the lens placode and devoid of nuclei, and outer 2/3rds layer
[germinative or proliferative layer] with nuclei and short process project into optic
ventricle. Both of these layers rest on their respective basal lamina. Basal lamina of the
inner 1/3rd layer forms the inner limiting membrane. The outer 2/3rd-layer basement
membrane forms the Bruch’s membrane. These structures disappear at seventh week and
replaced by precursors of outer segments of photoreceptors in the 4th month.
The retinal maturation begins at the posterior pole and proceeds towards the periphery.
By 30 weeks the mitotic activity has ceased completely. The increase in area of the retina
is due to the maturation and growth of individual cells.
By 4-5weeks [embryo 12mm], inward migration of putative ganglion and Muller cells
from the outer layer of neuroepithelium, organize the neuroepithelium into outer and
inner neuroblastic layers. An acellular layer separates the two layers. It consists of cell
process and is called Transient layer of Chievitz. The inner layer becomes the nerve fiber
layer. It also forms future ganglion cells, Muller’s cell, and amacrine cells. The axon
from the ganglion cells grows toward the optic nerve head.
By 9th to 12th week the transient layer of Chievitz develops the definitive inner plexiform
layer and four major horizontal layers of the retina. By 10th week the outermost cells of
the outer neuroblastic layer begun to develop the cones. The primitive layer of external
limiting membrane is formed by the lateral surfaces of these cells and zonulae adherents’
junctional complexes. The remaining component of the outer neuroblastic layer forms the
outer nuclear layer. A new inner nuclear layer with amacrine and Muller cells is present
at the posterior pole. The zone between the outer nuclear layer and inner nuclear layer
form the new outer plexiform layer. By 14weeks [70mm] the Amacrine cells develops
from the inner border of the outer neuroblastic layer. The transient layer of Chievitz
obliterates. Bipolar cells and horizontal cells don’t differentiate in the inner nuclear layer
until week 23rd.

Macula and fovea development.

Macular development is characterized by a localized superimposition of ganglion cell
nuclei at the posterior pole temporal to the optic disc during the 5th month of
development. By the 6th month of gestation there are eight or nine layers of nuclei. But
peripheral displacement of ganglion cells caused by axonal elongation commences by the
7th month creates formation of foveal depression. By 8th month there is approximately two
layers of ganglion cell. The foveal cones increase in length but decrease in width, so
increasing their density. Because they are not fully developed until several months after
birth the newborn infant has imperfect central fixation. At term a single layer of ganglion
cells is present and an internal nuclear layer overlying the macula cones, these are
displaced by the fourth month of life, leaving the central cones " uncovered."
 Even after 1 week after the birth, the thick cones still lack outer segments.
 The transient layer of Chievitz is not lost completely until nearly 4 years of age.

Peripheral retina.
By 4th month the future oraserrata becomes apparent and definite parsplana and oraserrata
apparent at 6th month. At the same time the peripheral retina has only thin nerve fiber
layer. The temporal region of the retina develops between 8th and 9th months. The
remaining portion and the indentation of the remaining retina develops after birth. The
zone between the ora and the equator enlarges in size until about 2 years of the age. At
birth the area of the retina is approximately 600mm2 and reaches 800 by 2 years.
Development of retinal vasculature.
At 4th month spindle shaped mesenchymal cells arise from the hyaloid artery where it
enters the optic disc. Mononuclear phagocytic cells play a role in angiogenesis. Pericytes
are present from early stage and they are from neural crest cells. The developing
vasculature is surrounded by basal lamina. Vascularization proceeds from the center to
periphery. On the temporal aspect of retina [superiorly and inferiorly] patent vessels are
present by 5th month. At this stage Vascularization is less extensive. Between 24 and 26
weeks, small blood vessels develop at ganglion layer. Primitive capillaries reach the
oraserrata by the eight-month. Full mature pattern of Vascularization is not attained until
3 months after birth.

Development of RPE.
The retinal pigment epithelium develops from the outer wall of the optic cup at 6 weeks
[20mm]. It is composed of mitotically active pseudostratified columnar epithelial cells
with ciliated inner surface. By 8th week [27-31mm] the retinal pigment epithelium has
single layer of hexagonal cells. During 3rd and 4th month [78-83mm] the cells become tall
cuboidal in shape and their nuclei spherical. By middle of 4th month, retinal pigment
epithelium is fully functional. The increase in surface are takes place after birth.
Appearance of melanin in embryonic RPE as early as 28 days after fertilization and the
same time cilia starts disappears.
Bruch membrane
Is well developed by 6th week [12-16mm]. Four or five layers are distinguishable by the
end of 9th week. The collagen fibers at 10 weeks, and the elastic fibers – 3.5 months.

Development of the optic nerve.

The optic nerve develops from the optic stalk, it has a connection with future third
ventricle and cavity of optic vesicle. At [4-4.5mm] 4 weeks gestation the stalk involutes
and forms the choroidal fissure or embryonic fissure. It starts constriction of proximal
portion – particularly on dorsal aspect. Neuroectodermal cells line it. It Incorporates
Hyaloid vessels and surrounded by Mesenchyme. Lips starts closing over near forebrain
[5-6 wk] and gradually extend distally [5-6wk] [12-17m]. Optic stalk closure follows that
of the optic cup and is dependent on breakdown of basal lamina, inversion of the outer
layers of the stalk, and regeneration of the basal lamina. Basal lamina that originally lined
the outer surface of fissure degenerates.. At 6 wk the nerve contains numerous axons,
Hyaloid artery and Hyaloid veins. By the seventh week of development the optic stalk is
full of nerve fibers, but Myelination doesn’t commence until the seventh month. Axon of
ganglion cell change direction – towards brain in developing Neuroectodermal cells of
optic nerve Displacement of the nerve occurs nasally during the 3rd month by eye
enlargement on temporal side. At 9 wk. – Bergmeister’s papillae formed by glial cell +
remnant of Hyaloid vessels. The Outer layer of Mesenchyme forms the dura. Cells from
the inner stalk will either vacuolate to make way for ganglion cell neurons, or
differentiate to form glial cells. The cells of inner layer forms astroglia, oligodendroglia.
Myelination starts near chiasma at 7th month and stops at lamina cribrosa about 1 month
after birth. The optic chiasma forms at 7 and half weeks. Meningeal sheaths derived from
neural crest mesoderm appear in the fifth month and invest the nerve in pia, subarachnoid
and duramater. Owing to the positioning of the optic fissure, defects in its closure result
in inferotemporal colobomas.
 50% growth – 20 wk.
 75% growth – by birth
 95% growth before the age of 1 year.

Malformations.
1. Coloboma. Inferionasally- associated with scleral ectasia.[ bulging of sclera]
2. Axial Coloboma. Or Morning glory syndrome.
 unilateral or bilateral
 Symmetrically enlarged or excavated optic disk.
 Similarity to American flower.
 Severe visual dysfunction
 Retrodisplacement of optic nerve into meninges of the optic nerve.
 Lamina cribrosa not formed.
 Defect in mesodermal organization in the disk

3)Surface ectoderm differentiation

The surface ectoderm forms

 The epithelium of the cornea,
 The epithelium conjunctiva
 The eyelids
 The Tarsal glands.
 Lacrimal glands.

a)Lids.

At 4-5 weeks [8-12mm] of gestation, the surface ectoderm forms the upper eyelid.
During the 2nd month [at 20mm] both upper and lower eyelids become evident. At the
beginning of the third month both margins are in contact with each other. Eyelids
develop from two ectodermal or cutaneous folds containing cores of mesenchyme
i.e. frontonasal and maxillary processes . Ectoderm of skin proliferates in the
region of the future eyelid ~ 4-5 weeks.
At about 2nd month, both eyelid prominences are visible.
~ 3rd month, eyelids meet and fuse until ~ 6th month where they separate
completely by the 7th month.
Orbicularis derives from the mesenchyme of the 2nd pharyngeal arch which
invades the eyelids ~ 3rd month.Approximately at 10 weeks [35-40mm] both margins.
Mesodermal mesenchyme invades the lids and differentiates into the palpebral
musculature. The upper lids arise from the fronto-nasal process whereas the lower eyelids
from the maxillary process. By the 10-week-old the embryo has already developed tarsal
glands.

b.) Lens.
The lens is formed from a disc shaped thickening of the surface ectoderm overlying the
optic vesicle on day 27 of development [4 –4.5 mm]. This is known as the lens placode.
Lens vesicle becomes separated from the surface ectoderm at the 33rd day gestation [8-10
mm] and contains a single layer of epithelial cells. Substances [fibroblast growth factor]
from the optic vesicle are thought to induce placode cells to elongate so forming the lens
vesicle on day 33.
During embryonic development ,the lens first takes form as a hollow ball of cells
.Each cell contains a nucleus which contains chromosomes that contain DNA, the
genetic material .The ball of the cells is oriented in the developing eye in such a
way that one surface is oriented in the developing eye in such a way that one
surface is pointing toward the outside of the eye and the opposite surface is
pointing toward the interior of the eye.

The lens capsule [non-cellular envelope] is derived from surface ectoderm. Cells from
the posterior part of vesicle lengthen, to form primary lens fibers that fill the vesicle
lumen. The secondary lens fibers arise from the anterior epithelial cell, and migrate and
taper to form the characteristic Y shaped [anterior] and inverted Y shaped [posterior]
sutures. Apices of posterior cell grow toward anterior lens epithelium. Tips of secondary
lens fibers surround primary lens epithelium to meet at Y shaped anterior and posterior
lens sutures. Nuclei migrate forward within elongated cell to form bow. Bow has
conspicuous convexity. Cells at equator continue to divide throughout life. Lens
continuous grows throughout life. [Thickness 0.02 mm each year]. Every subsequent
generation of fibers added to superficial to the previous layer. Eventually primary lens
fibers lose their nuclei become embryonic nucleus of adult.
So embryonic nucleus is formed from the primary lens fibers. The fetal nucleus arises
from the secondary fibers. Initially the anteroposterior diameter of the fetal lens
[spherical in shape] is greater than the equatorial diameter, but this situation slowly
reverses.
The nourishment for rapidly developing lens is provided by the hyaloid artery
entering a groove in optic vesicle which run forward to posterior lens surface to
form tunica vasculosa lentis at the end of 5th week, becoming most prominent ~
60mm stage and regresses ~ 240mm stage.
Zonnules of zinn develop from neuroepithelium. [65-mm stage]. Zonules are first seen
lying within the base of the secondary vitreous passing through tunica vasculosa
lentis to reach lens capsule ~ late 3rd month.
Lentropin is insulin like growth factor helps for fiber differentiation. Male lens is heavier
than female 8%

Malformations.
 Rubella – congenital cataract.
 Small lens- microphakia.
 Round lens. Spherophakia.
 Anterior lentiglobus.
 Posterior lentiglobus.

4)Neural crest cells – differentiation

Neural crest cell is mesoectoderm. They have diverse role in head and neck development.
They develop from junction of neuroectoderm and surface ectoderm of fore, mid, and
hind brain regions before the fusion of neural folds. They migrate in highly ordered
manner to pharyngeal arches, fore brain, developing optic cup and the facial region.
They give rise to,
 Bone.
 Cartilage.
 Connective tissue.
 Meninges
 Ocular and periocular connective tissue.
 Melanocytes.
 Dorsal root ganglia.
 Parasympathetic ganglia.
 The sensory ganglia [dorsal root ganglia] of both spinal and cranial nerves
 Odontoblasts,
  Schwann cells,

a)uvea.

Iris
Source :- i )mesoderm -stroma and vessels
ii) neuroectoderm- anterior and posterior iris epithelium

 Precursors of iris,i.e mesoderm at the edge of optic cup and the doubled
-layered neuroectoderm are evident ~ 6th week.The anterior chamber is
bounded by the anterior avascular corneal endothelium and a posterior thin
vascularised mesenchyme (anterior portion of the tunica vasculosa lentis )
which serves to be the future pupillary membrane.The doubled layered
neuroepithelium extend over the posterior surface of this pupillary
membrane and fuses with it to form the iris.
 ~4th month, sphincter pupillae begins to differentiate from the anterior
epithelial layer .
 ~6th month,sphincter pupillae begins to separate from the anterior epithelial
layer to move into stroma.
 At the end of 6th month, dilator pupillae differentiates from the anterior
epithelial layer.Nuclei and pigment granules are displaced apically while
cytoplasmic extensions with many myofilaments protrude into
stroma.Connective tissue septa and capillaries invade muscle bundles and
separate sphincter from dilator pupillae.
 Degeneration of pupillary membrane over the central part of iris forms the
pupil~ 8th month.

Normal iris development is dependent on the closure of the embryonic fissure, which
occurs on days 33-35; abnormal closure results in iris coloboma and / or hypoplasia.
By the sixth week of development the cornea and the tunica vasculosa lentis have formed
the anterior chamber boundaries. With the pupillary membrane the tunica vasculosa lentis
will form the primitive iris stroma that is infiltrated in the third or fourth months by the
long posterior and anterior ciliary arteries. During the fifth month the pupillary
membrane remodels itself and at the sixth month the central portion is absorbed, forming
the pupil. The sphincter and dilator muscles and the bilayered iris epithelium are derived
from neuroectoderm.
Both the iris muscle and its bilayered epithelium are derived from neuroectoderm. The
sphincter and dilator muscles arise later and are first seen as outgrowths from the basal
processes of epithelial cells that lie peripheral to Von Michel’s spur. Sphincter develops
before dilator muscle. The posterior epithelium does not give rise to any muscular
processes and is originally unpigmented, but during the fourth month of gestation
pigmentation begins at the pupil margin and spreads peripherally. At 14-15th week –
Sphincter muscle is [circumferential]- anterior iris pigment epithelial cells de laminate,
loose their melanin, develop intracytoplasmic microfilaments and dense bodies and
deposit basal lamina. Cell to cell contact [gap junctions] among the smooth muscle cell
not fully establishes until 7 months. At 6 months dilator muscle [radial]- Basal extensions
of anterior or pigmented epithelial layer. It develops even after birth. Never fully
independent of the epithelium.
Posterior iris epithelium.
 During development largely amelanotic.
 Continue with non-pigmented epithelium of CB.
 Intracytoplasmic melanin increases in 4th month, near pupillary margin
 7-8 month heavily pigmented.
Iris innervation.
Adrenergic and Cholinergic – not established until late in development. Full pigmentation
and the pattern of anterior surface not complete until a few years of postpartum.
Malformations.
Aniridia.
 Rare
 Autosomal dominant.
 Bilateral
 Absence of iris.
 Stump of hypercellular stroma with abnormal proliferation of pigment epithelium.
 Malformation or hypoplasia of outflow system.
 Anterior and posterior cortical lens opacities.
 Ectopia lentis.
 Hypoplastic optic nerve.
 Deletion of short arm of chromosome 11. [11p]
 Gene of nephroblastoma.
 AGR. Aniridia- G.U abnormalities- mental retardation.
 Anridia keratopathy.

Ciliary body.
Sources of development:-
i) mesoderm >ciliary smooth muscle ,stroma ,vessels,zonules
ii) neuroectoderm>NPE and PE of ciliary epithelium.

 ~3rd month : forward growth of anterior optic cup margin lacks behind
retina in differentiation and it is thought that the tips of the optic cup
must contact the lens in order to differentiate into ciliary body and iris .
Development of ciliary processes is evidenced by the formation of
longitudinal oriented ridges adhere to the inner nonpigmented layer and
fold with it forming ~ 70-75 radial folds.Differentiation of stroma elements
begin with the accumulation of mesenchyme between the growing margins
of the optic cup and surface ectoderm.
 Late 3rd month :-Primary ciliary muscle fibers are seen within the
mesenchyme between the infolding region and scleral condensation.
 ~4th month :- irregular capillary -venous network surrounding anterior
portion of the optic cup give rise to invading buds which penetrate into
mesenchyme that forms core of the growing ciliary processes.These buds
 consists of endothelial ridges which later canalise.Also, Long posterior
ciliary arteries form the major arterial circle.Ciliary body is formed and
ciliary muscle becomes organized into fibers .
 ~5th month :- the triangular meridional portion differentiates and the anterior
ends of the fibers are continuous with the developing scleral spur.
 ~6th month :-the circular fibers appear on the inner aspect of the
meridional muscle.
 ~7th month :- muscle bundles increase in size and organization but are still
incompletely formed at birth.Growth of eyeball elongates pars plana such
that ora serrata which is even at midpoint of ciliary body comes to lie at
a level with its posterior 3rd ~ 9th month.
The Ciliary body is derived from neuroectoderm and mesenchyme. It commences in 11 –
12th week with indentation of the outer pigmented layer of neuroectoderm by small
capillaries in the inner vascular mesenchyme. The Ciliary epithelium is formed from the
anterior edge of the optic cup but doesn’t differentiate like the rest of the retina,
approximately 3 months of gestation. Initially, the inner nonpigmented ciliary epithelium
is flat, but as the vascular sprouts enlarge they push inwards to form primitive radial
folds. This epithelium is thrown into folds, forming the ciliary process, and from fourth to
sixth differentiation occurs to produce tight junctions and interdigitations. Between 14
and 22 weeks 70-75 radial folds increase in height and complexity. The Ciliary
epithelium commences aqueous production as early as 20 weeks. The ciliary stroma is
formed from the mesenchyme lying between the optic cup and cornea, with primitive
muscle being visible at 3 months. Circular or radial muscle fibers don’t differentiate until
much later in development and indeed are not fully formed until about 1 year of age.
During the fourth month a primitive scleral spur appears which is not fully formed until
after the first year of life.

Choroid.
 ~ 4th week :- condensation and differentiation of mesoderm outside
developing RPE into endothelial cells and choriocapillaries.
 ~5th week:- vascular plexus appears over whole of optic cup, appearance of
vortex veins .
 3rd month:- definite emergence of chooriocapillaries.
 4th month :- formation of Haller’s layer of larger vessels.
 5th month :- formation of Sattler’s layer of mainly arterial vessels between
choriocapillaries and larger channels sclerad.
[Except for the vascular endothelium; all of the choroid (vascular smooth muscle
cells, fibrocytes ,melanocytes) derives from the cranial neural crest cells.]
The choroid develops early from the differentiation of loose mesenchyme that
surrounding the optic cup. Choroidal development is dependent on the vascular
framework that develops around the long and short posterior ciliary arteries. A palisade
layer of vessels that lie external to RPE forms the basis for the future choriocapillaries. A
second layer at 4 months extends to future choriocapillaries to form rudimentary vortex
veins. During 5th month an intermediate layers forms future sattler’s layer. The
condensation of neural crest cells around the anterior margin of the optic stalk forms cells
of choroidal stroma. Melanoblasts from the neural crest invade the Choroidal
mesenchyme during the seventh month, mature and form melanocytes.
 Differentiation of choriocapillaries begins simultaneously with that of the retinal
pigment epithelium during the fourth and fifth week of gestation.
 Diaphragmed fenestration, characteristic of the choriocapillaries, are first
recognized after 7th week of gestation and more numerous during the ninth week.
 Pericytes are detected as early as the sixth week of gestation.
 By the end of second month, arteriolar channels [branches of the future short
posterior ciliary arteries] can be distinguished by their narrow lumen and walls of
two or more cells.
 During the 3rd or 4th months definitive layering of the choroidal vasculature
becomes apparent with the development of the outer [sclerad], large vessel layer
[of Haller].
 During the 4th month the long ciliary arteries form the major arterial circle.
 By the 5th month recurrent branches from the major arterial circle extends into the
ciliary body.
 Final anastomosis with the arterial circulation of the choroid is not established
until 8th month of gestation.
 Choroidal stroma begins the second trimester and by the end of the third month it
is demarcated by the sclera.
 Elastic tissue in stroma is first seen 4th month.

Sclera.
Scleral is developed from the mesenchymal cells around the optic cup. These cells are
neurocrest in origin. Precursors of sclera are evident ~ 7th week gestation.At 6 weeks
development proceeds in anteroposterior direction.Posterior pole condensation occurs
~ 9th week. . Sclera also develops from inside outward.Long axis of mesodermal
cells arrange parallel to surface of optic cup and initially extends as far as recti
insertions.
By the middle of the 7th week demarcation of sclera from the surrounding tissues is
apparent. At 9th week of gestation deposits of collagen is recognizable. By 11th week cells
almost attained adult appearance and at the same time lamina cribrosa forms. At the
beginning of 4th month, the sclera in both pre-and post equatorial regions consists of 30
cell layers, this increases to 50 layers by the 6th month, after which time no further
mitoses are seen. At approximately 4 months [70mm] the inner aspect of the anterior
sclera develops a fibrous wedge-shaped protrusion the sclera spur. By 5 months the sclera
is fully formed.
By the middle of the 7th month the anterior ends of the longitudinal ciliary fibers have
established their insertion into the sclera spur. The deep and intrascleral vascular plexus,
the aqueous veins and the collector channels that traverse the sclera are first recognizable
at about 12 weeks.

b)cornea
Corneal development begins at day 33 of gestation, after the lens cup has separated from
the surface ectoderm. The initial step in corneal development is the production of a
bilayered epithelium and thin basement membrane separate from a bilayer of endothelial
cells and associated basement membrane.
The corneal epithelium is derived from surface ectoderm, where as the endothelium
[around 33 days] and fibroblasts that produce the corneal stroma [around 49th day, 22-24
mm] are derived from neural crest cells. The substantia propria of the cornea is derived
from the anterior part of the same mesodermal layer that forms the sclera. This mesoderm
is in close contact with the surface ectoderm which forms the epithelium covering the
superficial surface of the cornea. The final diameter of the cornea is determined by the
diameter of the optic cup.
At approximately 7 weeks gestation a primitive stroma is formed, which is infiltrated by
fibroblasts producing collagen fibrils. By the third month the stroma is a structure or 25-
30 layers, a thin Descemet’s membrane is present and the endothelium is now a single
layer. The fetal cornea is very hydrated to the adult form and is therefore translucent
rather than transparent. By 5 months the corneal nerves [commences at 3 months] are
present and at 7 months the cornea has reached its adult form.
 Around 8 weeks – first evidence of loosely arranged collagen fibers.
 Layer of wing cell of epithelium doesn’t appear until fourth month or fifth month.
 Bowman’s membrane [always acellular] becomes identifiable by 5 months.
 Descemet’s membrane is demarcated clearly by 6th month.
 Keratin’s sulphate not detected until 6 months of gestation.
 Maturation process of collagen lamella and keratoblasts commences in the
posterior layers and progress more anteriorly.
 The diameter of cornea increases from 2 mm at 12 weeks gestation to 3.5 mm at
15 weeks, 4.5 mm at 17 weeks, 5.5 mm at 21 weeks and 9.3 mm at 35 weeks.
 Corneal thickness and diameter continue to increase throughout development by
both interstitial growth [thickening of lamella] and appositional growth [addition
of lamella].
Anomalies.
 Scleralization of the cornea.
 Peter’s anomaly.
 Embryotoxon.
 Axenfield’s anomaly.
 Rieger’s anomaly.

c)chamber angle
The anterior and posterior chambers of the eye (aqueous chamber) are formed by a
splitting of the mesoderm in the region, and correspond to the subarachnoid space of the
brain. The mesodermal cells lining the cavity give origin to a flattened mesothelium.

5)Vascular system

The blood vessels of the eyeball are formed in the mesodermal layer that is a continuation
of the pia-arachnoid. The mesenchyme forms the choroid and contributes to the ciliary
body and iris.
Part of the mesoderm that gets invaginated into the optic cup forms the retinal vessels.
The central artery and vein of the retina at first lie in the choroidal fissure, but come to b
buried in the fibres of the developing optic nerve. As the choroidal fissure extends for
some distance along the optic stalk, the central artery of the retina runs through the
substance of the distal part of the optic nerve.
Initially, the lens is completely surrounded by a vascular capsule. The posterior part of
the capsule is supplied by the hyaloid artery. This artery is a continuation of the central
artery of the retina and passes through the vitreous. Later in fetal life, the vascular
capsule and the hyaloid artery disappear.

Development of Vitreous.
The development of vitreous is associated with the development of hyaloid artery.
At 4 weeks [5-7mm] stage, mesodermal cells invade the cavity of the developing optic
cup through the patent optic fissure. These cells differentiate into hyaloid artery and vasa
hyaloidae propia.
Primary vitreous.
Between 4th and 5th week [13 mm stage], the primary vitreous occupies the letrolental
space with fibrilar material, mesenchymal cells, and vascular channels. The fibrilar
material is ectodermal in origin. The mesenchymal cells differentiate the fibroblasts and
mononuclear phagocytes from the hyaloid artery. The primary vitreous attains the
maximum formation by 2 months gestation. By 5th month [16-mm stage] hyaloid artery
forms the capillary network to join the fibrilar capsule on the posterior surface of the lens.
Secondary vitreous.
The secondary is avasular and starts developing at 13-mm stage, continuos until the 70-
mm stage. It consists of type 2 collagen fibers and it occupies between retina and primary
vitreous.
Tertiary vitreous.
This other wise called embryonic zone of origin or vitreous base. It develops at 12weeks
[65mm] from the condensation of thicker collagen fibers of the secondary vitreous.
Tunica vasculosa lentis.
At 9th month [35mm] vascular vessels grow from the rim of the optic cup toward the
equator and anterior surface of the lens. They organized as capsulopupillay vessels. The
tunica vasculosa lentis reaches its greatest development at 40mm stage. By 4th month
atrophy of the hyaloid artery and simultaneous retraction of the primary vitreous occurs.
They confined to retrolental space. This area remains throughout life as cloquet’s canal.
Final organization of the vitreous.
At 5th month [160mm] the pupillary membrane and the posterior vascular capsule on the
anterior and posterior surfaces of the lens regress. At 7th month blood flow in the hyaloid
artery ceases and completely atrophied by birth. The phagocytes in the cortex of the
vitreous begin to synthesize hyaluronic acid.
 Surface ectodermal derived elements also contribute.
 Primary vitreous is mixed - ectodermal + mesenchymal origin.
 Secondary vitreous is avascular.
 Mesenchymal cell in adventia of vitreous vessels – vitreous matrix.
 After birth- much of hyaluronic acid and collagen [type 2] added.
 Tertiary vitreous. - Fibers firmly attached in developing pars plana region – when
they mature they form vitreous base.
 Non-pigmented epithelium of ciliary body are responsible for tertiary vitreous +
Zonular fibers.
 Macrophages scavengers role in regression of Hyaloid vessels.
Malformations.
 Regression of Hyaloid system doesn’t occur.
 Dense vascularized collagenous tissue contracts and deforms.
 Persistence of tunica vasculosa lentis or pupillary membrane.
 Persistence of hyperplastic primary vitreous.
 Ciliary processes are drawn internally.
 Persistence hyperplastic primary vitreous.
 Persistence Hyaloid artery.
 Condensed posterior primary vitreous.
 Distortion of the disc and retina.
 Prepapillary and preretinal fibrous membrane.
 Radial or falciform folds in the retina.

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
Embryology by Prasad
 Chronological sequence of events in the formation of the eye.
 Developmentally and functionally the eye is an extension of the central nervous system.
Eye develops from surface ectoderm, neural ectoderm, neural crest, and mesodermal
mesenchyme. The development of the eye starts around the 22nd day. It is essential to
know the development of the embryo in first 21 days.
Development of embryo.
A. Events of first 3 weeks. [21 days]

First week. [7 days]

The male and female gametes unite at fertilization within the oviduct. It is diploid cell,
called zygote. This zygote undergoes cleavage as it travels towards the uterus. In 30-cell
stage [morula] the cavity appears in the zygote [blastocyst cavity.]. At this stage a
peripheral outer cell mass [trophoblast] and inner cell mass [embryblast] are formed.
The embryoblast is heterogeneous collection of cells and it leads embryo proper. The
trophoblast differentiates into syncytio and cytotrophoblast, which contributes to the
development of fetal component of the placenta. By day 5 or 6, the embryo is a hollow
spheroid of around 100 cells [blastocyst]. Around this day the blastocyst commences
implanting to the endometrial lining of the uterus.
2nd week. [From 8th day]
Two cavities appear in the embryo proper [embryoblast]. The [1.] amniotic cavity is lined
by the epiblast cells, and the [2.] yolk stalk lined by the cells of hypoblast. There is
double layer formation at the impinge of these two layers, called primary ectoderm
[epiblast] and primary endoderm [hypoblast]. At this stage it is a bilaminar disc. This
leads to proper embryo.
3rd week. [From 15th day]
At the caudal end of the primitive ectoderm [epiblast], there is a formation of primitive
streak or primitive knot. From here the primary ectodermal cells detach and migrate
laterally and cranially into the space between ectoderm and endoderm to form third germ
layer [intraembryonic mesoderm] and some cells replace the original hypoblast to form
the definitive or secondary hypoblast. Formation of the primitive streak establishes the
craniocaudal axis and bilateral symmetry of the future embryo.
The formation of the notochord on the primitive streak induces the formation of the
neural plate. By the paraxial mesodermal condensations [somites] along the neural plates,
the neural tube is formed. The neural tube is the precursor of the central nervous system.
A special cells, [neural crest cells] detach from the margins of the neural folds and
undergoes extensive migration.
At 22nd day, the embryo is 2-mm length with eight pairs of somites.
Development of eye and other from 22nd day as follows,
Day. 22nd. [2 – 3 mm]
 Optic sulci.
  Neural crest.

 Surface ectoderm.

 Mesoderm/somitomeres.

 
Day. 27th [4-5mm]
 Optic vesicle.

 Neural crest cells steaming over the optic cup and stalk.

 Lens placode.

 Retinal disc.

 Cavity of the optic vesicle.

 Optic stalk with cavity.

 Pharyngeal arches and clefts.

 Heart bulge.

 Umbilical cord.

Day 29. [6-7mm]

 Condensed mesenchyme around the optic cup.

 Optic cup rim.

 Lens vesicle.

 Lens pit.

 Hyaloid vessels.

 Maxillary swelling.

 Mandibular swelling.

 Nasal and frontal prominences.

 Limb buds.

 
Day. 37th [8-11mm]
 Future corneal epithelium.

 Primary lens fibers.

 Future neural retina.

  Future RPE

 Futuresubretinal space.

 Ear swellings.

Day 44. [13-17mm]

 Lids forming.

 Future corneal endothelium and stroma.

 Tunica vasculosa lentis.

 Hyaloid artery.

 Developing sclera.

 Developing choroid.

 
Day 50th [20-30mm]
 Conjuctival sac.

 Lid fusion.

 Anterior chamber.

 Cornea

 Vitreous

 Ganglion cells in optic nerve

 Ganglion cells.

 Optic nerve sheaths.

1. Neuroectodermal differentiation.

Since eye is an extension of the central nervous system, a few considerations of the
development of the central nervous system are considered here.
Neural ectoderm give rise to
 Retina and retinal pigment epithelium.

 Sphincter and dilator pupillae

 Posterior pigment epithelium of the iris

 The neural portion of the optic nerve and chiasma.

The ectoderm on the dorsal surface of the embryo forms a thickness in the mid-region to
form the neural or medullary plate. These cells are called as the neural ectoderm. By 18
days a central depression developed in the neural plate [neural groove] and lateral plates
[neural folds]. The two walls fuse to form the neural tube. The fusion begins in the mid-
region and progress both anteriorly and posteriorly. Before the closure of the neural tube
at the anterior end, the same neural folds develops small lateral grooves [optic sulcus] to
represent future eyes at the anterior end of the embryo. This optic sulcus enlarges to form
the optic evaginations to become the optic vesicles. These optic vesicles are in contact
with the surface ectoderm externally.
In the region of the future neural folds, the neuroectodermal cells proliferate to produce a
population of neural crest cells. These cells play an important role in the development of
the eye. Most of the neural crest cells migrate away from the neural tube to differentiates
many body structures including cephalic cartilages, bones and ligaments, leptomeininges,
dental papillae, schwann cells, peripheral sensory and autonomic nerves, ganglia or
cranial nerves 5, 7 9 and 10, spinal ganglia, dermis and melanophores of the skin and
many cells of the endocrine system. The cells that remain attached to the neural plate
differentiate into the cerebral and spinal ganglia and the roots of the dorsal nerves.
Development of opticvesicle.
Is a hollow, symmetrical, hemispherical outgrowth on the lateral wall of the forebrain
vesicle. It is lined by high columnar with nuclei arranged in several layers. The cells of
the inner surface are ciliated. The outer surface of the cells is covered by a thin basal
lamina. It is connected to the lower region by the optic stalk. These vesicles are separated
by the frontonasal process. In 19-mm embryo, the direction of growth makes an angle of
65 with the midsagittal plane, where as in the adult the corresponding angle made by the
optic nerve is 40 degrees.
By 28 days [embryo 7.6-7.8], invagination of the optic vesicle and optic stalk takes place.
In the process of invagination, differential growth and movement of the cells causes the
temporal and lower walls to move inward against the upper and posterior walls.
The cavity of the optic vesicle or optic ventricle [future subretinal space] is continuous
via the lumen in the optic stalk. This communicates with the future third ventricle.
By the end of the embryonic period [week 8] the optic vesicle leads to the formation of
the thin layer [future retinal pigment epithelium] and thicker inner layer [future inner
retina]. The optic vesicle is formed by a lateral out-pouching from the diencephalon and
is fully formed by day 25. The proximal portion of the optic vesicle becomes constricted
to form the optic stalk and the dilated distal segment forms the optic cup, both become
involuted during the fifth week producing a groove on their inferior aspects [known as
the optic or choroidal fissure]. The hyaloid artery and surrounding vascular mesenchyme
are enclosed in the optic fissure. The optic cup closes in the fifth week, followed by
closure of the optic stalk that proceeds from the forebrain towards the cup in week six.
 
The optic vesicle consits of an outer and inner layer. The outer layer is composed of
pseuostratified columnar cells with pigment granules being present as early as the third
week of gestation, this layer will form the retinal pigment epithelium. The inner layer
[which will form the neural retina] consits of an outer nuclear and inner marginal zone.
Mitosis is maximum in the outer zone of inner layer and is completed by 15 weeks,
wheras the cells of future retinal pigment epithelium continue to divide late into fetal life.
As mitosis finishes differentiation begins, this is initiated in the marginal zone. The cilia
found in the outernucler zone of inner layer disappears by the seventh week.
By 7 week of gestation the neural epithelium has separated into inner and outer
neuroblastic layers. The inner layer will produce ganglion and amacrine cells whereas the
outer layer gives rise to horizontal and bipolar elements. Lamination is essentially
complete by 4 ½ months and the oraserrata by 6 months. Photoreceptors are thought to be
derived from cilia found in the outer nuclear zone.
 
 
 The optic vesicle is surrounded by the Mesenchymal cells except at the apex of the vesicle, which
is closely apposed to the surface ectoderm.

 Lens placode formation coincides with formation of a constriction in the optic vesicle at its
attachment to the wall of the forebrain to form the optic stalk.

 The active growth of the optic cup is not uniform around the circumference.

 By 29 day the invagination of the retinal disc complete.

 
Optic stalk. [Embryonic, fetal, choroidal or optic fissure]
It is surrounded by a basal lamina. The margin of the fissure comprises the inner neural
retina [consists of several layers] and single layer of retinal pigment epithelium. In the
early stage of fusion the outer layer of the cup become inverted into the fissure. The
longitudinal groove of the optic stalk which extends into the optic stalk, acts as a
temporary deficiency in the cup through which vascular mesenchyme and a branch of the
ophthalmic artery, becomes incorporated into the fissure and thus gain access to the
growing lentoretinal space. The fusion of the optic stalk commences at the midportion of
the optic stalk and continuous both proximally and distally. By the end of sixth week the
growing edges of the choroidal fissure meet and fuse with hyaloid vessels and associated
mesenchyme in the center. Distally the fused margins form the pupil and proximally it
forms the entry point for the central retinal artery and vein.
 
 
Congenital malformations of optic vesicle and fissure.
Coloboma.
 As the result of a failure of closure of the inferio- nasal optic fissure fusion.

Coloboma of iris.
 Inferior nasal defect in stroma, smooth muscle and pigment epithelium.

Ciliary body Coloboma.

 Absence of ciliary process.

 Presence of diminutive muscle

 Adjacent lens indented.

 Failure of formation of Zonular fibers.

Coloboma of Retina.
 In adjacent retina proliferation of neuroblastoic tissue leads to the formation of rosettes.

 Absence of Bruch membrane and choroidal tissue.

 Underlying sclera normal.

 Glial and vascular Ingrowth from the retina across the bed of Coloboma.

Development of the Retina.

 
At 26 days of gestation [4mm] the inner layer of the optic vesicle undergoes mitosis to
form 3 or 4 layers of compact cells. By 32-33 days the retina consist of 5 or 6 layers of
neuroepithelial cells. This is divided into inner 1/3rd and outer 2/3rd. The inner layer [inner
marginal layer] faces the lens placode and devoid of nuclei, and outer 2/3rds layer
[germinative or proliferative layer] with nuclei and short process project into optic
ventricle. Both of these layers rest on their respective basal lamina. Basal lamina of the
inner 1/3rd layer forms the inner limiting membrane. The outer 2/3rd-layer basement
membrane forms the Bruch’s membrane. These structures disappear at seventh week and
replaced by precursors of outer segments of photoreceptors in the 4th month.
The retinal maturation begins at the posterior pole and proceeds towards the periphery.
By 30 weeks the mitotic activity has ceased completely. The increase in area of the retina
is due to the maturation and growth of individual cells.
By 4-5weeks [embryo 12mm], inward migration of putative ganglion and Muller cells
from the outer layer of neuroepithelium, organize the neuroepithelium into outer and
inner neuroblastic layers. An acellular layer separates the two layers. It consists of cell
process and is called Transient layer of Chievitz. The inner layer becomes the nerve fiber
layer. It also forms future ganglion cells, Muller’s cell, and amacrine cells. The axon
from the ganglion cells grows toward the optic nerve head.
By 9th to 12th week the transient layer of Chievitz develops the definitive inner plexiform
layer and four major horizontal layers of the retina. By 10th week the outermost cells of
the outer neuroblastic layer begun to develop the cones. The primitive layer of external
limiting membrane is formed by the lateral surfaces of these cells and zonulae adherents’
junctional complexes. The remaining component of the outer neuroblastic layer forms the
outer nuclear layer. A new inner nuclear layer with amacrine and Muller cells is present
at the posterior pole. The zone between the outer nuclear layer and inner nuclear layer
form the new outer plexiform layer. By 14weeks [70mm] the Amacrine cells develops
from the inner border of the outer neuroblastic layer. The transient layer of Chievitz
obliterates. Bipolar cells and horizontal cells don’t differentiate in the inner nuclear layer
until week 23rd.
Macula and fovea development.
Macular development is characterized by a localized superimposition of ganglion cell
nuclei at the posterior pole temporal to the optic disc during the 5th month of
development. By the 6th month of gestation there are eight or nine layers of nuclei. But
peripheral displacement of ganglion cells caused by axonal elongation commences by the
7th month creates formation of foveal depression. By 8th month there is approximately two
layers of ganglion cell. The foveal cones increase in length but decrease in width, so
increasing their density. Because they are not fully developed until several months after
birth the newborn infant has imperfect central fixation. At term a single layer of ganglion
cells is present and an internal nuclear layer overlying the macula cones, these are
displaced by the fourth month of life, leaving the central cones " uncovered."
 Even after 1 week after the birth, the thick cones still lack outer segments.

 The transient layer of Chievitz is not lost completely until nearly 4 years of age.

Peripheral retina.
By 4th month the future oraserrata becomes apparent and definite parsplana and oraserrata
apparent at 6th month. At the same time the peripheral retina has only thin nerve fiber
layer. The temporal region of the retina develops between 8th and 9th months. The
remaining portion and the indentation of the remaining retina develops after birth. The
zone between the ora and the equator enlarges in size until about 2 years of the age. At
birth the area of the retina is approximately 600mm2 and reaches 800 by 2 years.
Development of retinal vasculature.
At 4th month spindle shaped mesenchymal cells arise from the hyaloid artery where it
enters the optic disc. Mononuclear phagocytic cells play a role in angiogenesis. Pericytes
are present from early stage and they are from neural crest cells. The developing
vasculature is surrounded by basal lamina. Vascularization proceeds from the center to
periphery. On the temporal aspect of retina [superiorly and inferiorly] patent vessels are
present by 5th month. At this stage Vascularization is less extensive. Between 24 and 26
weeks, small blood vessels develop at ganglion layer. Primitive capillaries reach the
oraserrata by the eight-month. Full mature pattern of Vascularization is not attained until
3 months after birth.
Development of RPE.
The retinal pigment epithelium develops from the outer wall of the optic cup at 6 weeks
[20mm]. It is composed of mitotically active pseudostratified columnar epithelial cells
with ciliated inner surface. By 8th week [27-31mm] the retinal pigment epithelium has
single layer of hexagonal cells. During 3rd and 4th month [78-83mm] the cells become tall
cuboidal in shape and their nuclei spherical. By middle of 4th month, retinal pigment
epithelium is fully functional. The increase in surface are takes place after birth.
Appearance of melanin in embryonic RPE as early as 28 days after fertilization and the
same time cilia starts disappears.
Bruch membrane
Is well developed by 6th week [12-16mm]. Four or five layers are distinguishable by the
end of 9th week. The collagen fibers at 10 weeks, and the elastic fibers – 3.5 months.
Development of the optic nerve.
 
The optic nerve develops from the optic stalk, it has a connection with future third
ventricle and cavity of optic vesicle. At [4-4.5mm] 4 weeks gestation the stalk involutes
and forms the choroidal fissure or embryonic fissure. It starts constriction of proximal
portion – particularly on dorsal aspect. Neuroectodermal cells line it. It Incorporates
Hyaloid vessels and surrounded by Mesenchyme. Lips starts closing over near forebrain
[5-6 wk] and gradually extend distally [5-6wk] [12-17m]. Optic stalk closure follows that
of the optic cup and is dependent on breakdown of basal lamina, inversion of the outer
layers of the stalk, and regeneration of the basal lamina. Basal lamina that originally lined
the outer surface of fissure degenerates.. At 6 wk the nerve contains numerous axons,
Hyaloid artery and Hyaloid veins. By the seventh week of development the optic stalk is
full of nerve fibers, but Myelination doesn’t commence until the seventh month. Axon of
ganglion cell change direction – towards brain in developing Neuroectodermal cells of
optic nerve Displacement of the nerve occurs nasally during the 3rd month by eye
enlargement on temporal side. At 9 wk. – Bergmeister’s papillae formed by glial cell +
remnant of Hyaloid vessels. The Outer layer of Mesenchyme forms the dura. Cells from
the inner stalk will either vacuolate to make way for ganglion cell neurons, or
differentiate to form glial cells. The cells of inner layer forms astroglia, oligodendroglia.
Myelination starts near chiasma at 7th month and stops at lamina cribrosa about 1 month
after birth. The optic chiasma forms at 7 and half weeks. Meningeal sheaths derived from
neural crest mesoderm appear in the fifth month and invest the nerve in pia, subarachnoid
and duramater. Owing to the positioning of the optic fissure, defects in its closure result
in inferotemporal colobomas.
 
 50% growth – 20 wk.

 75% growth – by birth

 95% growth before the age of 1 year.

Malformations.
1. Coloboma. Inferionasllay- associated with scleral ectasia.[ bulging of sclera]

2. Axial Coloboma. Or Morning glory syndrome.

 unilateral or bilateral

 Symmetrically enlarged or excavated optic disk.

 Similarity to American flower.

 Severe visual dysfunction

 Retrodisplacement of optic nerve into meninges of the optic nerve.

 Lamina cribrosa not formed.

 Defect in mesodermal organization in the disk

3. The surface ectoderm forms

 The epithelium of the cornea,

 The epithelium conjunctiva

 The eyelids

 The Tarsal glands.

 Lacrimal glands.

Mesoderm forms
 orbital walls

 Extraocular muscles.

 Tenon’s capsule

 Sclera

 Choroid

 Descemet’s membrane, Corneal stroma, Corneal endothelium

 Bowman’s membrane is an anterior stromal condensation.

 Iris stroma and anterior epithelium.

Development of muscles.
 
The muscles are not developed from neural crest origin. They thought to arise from the
presumptive myocytes in the preoptic region [paraxial mesoderm] in the area of
prechordal plate. They migrate ventrally and caudally around the developing eye. The
lateral rectus and levator palpebral superioris develops at week 5th. Superior oblique and
medial rectus develops at week 6th.
The following structures are of ectodermal origin
 Retina,

 Retinal pigment epithelium

 Epithelium of the ciliary body.

The following structures are derived from the mesenchyme

 The sclera,

 Iris stroma

 The ciliary body

4. Neural crest cells – differentiation

 
Neural crest cell is mesoectoderm. They have diverse role in head and neck development.
They develop from junction of neuroectoderm and surface ectoderm of fore, mid, and
hind brain regions before the fusion of neural folds. They migrate in highly ordered
manner to pharyngeal arches, fore brain, developing optic cup and the facial region.
They give rise to,
 Bone.

 Cartilage.

 Connective tissue.

 Meninges

 Ocular and periocular connective tissue.

 Melanocytes.

 Dorsal root ganglia.

 Parasympathetic ganglia.

 The sensory ganglia [dorsal root ganglia] of both spinal and cranial nerves

 Odontoblasts,

 Schwann cells,

Development of lids.
 
At 4-5 weeks [8-12mm] of gestation, the surface ectoderm forms the upper eyelid.
During the 2nd month [at 20mm] both upper and lower eyelids become evident. At the
beginning of the third month both margins are in contact with each other. Approximately
at 10 weeks [35-40mm] both margins. Mesodermal mesenchyme invades the lids and
differentiates into the palpebral musculature. The upper lids arise from the fronto-nasal
process whereas the lower eyelids from the maxillary process. By the 10-week-old the
embryo has already developed tarsal glands.
b. Lens.
The lens is formed from a disc shaped thickening of the surface ectoderm overlying the
optic vesicle on day 27 of development [4 –4.5 mm]. This is known as the lens placode.
Lens vesicle becomes separated from the surface ectoderm at the 33rd day gestation [8-10
mm] and contains a single layer of epithelial cells. Substances [fibroblast growth factor]
from the optic vesicle are thought to induce placode cells to elongate so forming the lens
vesicle on day 33. The lens capsule [non-cellular envelope] is derived from surface
ectoderm. Cells from the posterior part of vesicle lengthen, to form primary lens fibers
that fill the vesicle lumen. The secondary lens fibers arise from the anterior epithelial cell,
and migrate and taper to form the characteristic Y shaped [anterior] and inverted Y
shaped [posterior] sutures. Apices of posterior cell grow toward anterior lens epithelium.
Tips of secondary lens fibers surround primary lens epithelium to meet at Y shaped
anterior and posterior lens sutures. Nuclei migrate forward within elongated cell to form
bow. Bow has conspicuous convexity. Cells at equator continue to divide throughout life.
Lens continuous grows throughout life. [Thickness 0.02 mm each year]. Every
subsequent generation of fibers added to superficial to the previous layer. Eventually
primary lens fibers lose their nuclei become embryonic nucleus of adult. So embryonic
nucleus is formed from the primary lens fibers. The fetal lens arises from the secondary
fibers. Initially the anteroposterior diameter of the fetal lens [spherical in shape] is greater
than the equatorial diameter, but this situation slowly reverses. The nourishment is from
tunica vasculosa lentis [60-mm stage]. Zonnules of zinn develop from neuroepithelium.
[65-mm stage]. Lentropin is insulin like growth factor helps for fiber differentiation.
Male lens is heavier than female 8%
Malformations.
 Rubella – congenital cataract.

 Small lens- microphakia.

 Round lens. Spherophakia.

 Anterior lentiglobus.

 Posterior lentiglobus.

 
b. Cornea.
 
Corneal development begins at day 33 of gestation, after the lens cup has separated from
the surface ectoderm. The initial step in corneal development is the production of a
bilayered epithelium and thin basement membrane separate from a bilayer of endothelial
cells and associated basement membrane. The corneal epithelium is derived from surface
ectoderm, where as the endothelium [around 33 days] and fibroblasts that produce the
corneal stroma [around 49th day, 22-24 mm] are derived from neural crest cells. The final
diameter of the cornea is determined by the diameter of the optic cup. At approximately 7
weeks gestation a primitive stroma is formed, which is infiltrated by fibroblasts
producing collagen fibrils. By the third month the stroma is a structure or 25-30 layers, a
thin Descemet’s membrane is present and the endothelium is now a single layer. The fetal
cornea is very hydrated to the adult form and is therefore translucent rather than
transparent. By 5 months the corneal nerves [commences at 3 months] are present and at
7 months the cornea has reached its adult form.
 Around 8 weeks – first evidence of loosely arranged collagen fibers.

 Layer of wing cell of epithelium doesn’t appear until fourth month or fifth month.

 Bowman’s membrane [always acellular] becomes identifiable by 5 months.

 Descemet’s membrane is demarcated clearly by 6th month.

 Keratin’s sulphate not detected until 6 months of gestation.

 Maturation process of collagen lamella and keratoblasts commences in the posterior layers and
progress more anteriorly.

 The diameter of cornea increases from 2 mm at 12 weeks gestation to 3.5 mm at 15 weeks, 4.5
mm at 17 weeks, 5.5 mm at 21 weeks and 9.3 mm at 35 weeks.

 Corneal thickness and diameter continue to increase throughout development by both interstitial
growth [thickening of lamella] and appositional growth [addition of lamella].

Anomalies.
 Scleralization of the cornea.

 Peter’s anomaly.

 Embryotoxon.

 Axenfield’s anomaly.

 Rieger’s anomaly.

 
 
a. uvea.
 
Iris.
Normal iris development is dependent on the closure of the embryonic fissure, which
occurs on days 33-35; abnormal closure results in iris coloboma and / or hypoplasia.
By the sixth week of development the cornea and the tunica vasculosa lentis have formed
the anterior chamber boundaries. With the pupillary membrane the tunica vasculosa lentis
will form the primitive iris stroma that is infiltrated in the third or fourth months by the
long posterior and anterior ciliary arteries. During the fifth month the pupillary
membrane remodels itself and at the sixth month the central portion is absorbed, forming
the pupil. The sphincter and dilator muscles and the bilayered iris epithelium are derived
from neuroectoderm.
Both the iris muscle and its bilayered epithelium are derived from neuroectoderm. The
sphincter and dilator muscles arise later and are first seen as outgrowths from the basal
processes of epithelial cells that lie peripheral to Von Michel’s spur. Sphincter develops
before dilator muscle. The posterior epithelium does not give rise to any muscular
processes and is originally unpigmented, but during the fourth month of gestation
pigmentation begins at the pupil margin and spreads peripherally. At 14-15th week –
Sphincter muscle is [circumferential]- anterior iris pigment epithelial cells de laminate,
loose their melanin, develop intracytoplasmic microfilaments and dense bodies and
deposit basal lamina. Cell to cell contact [gap junctions] among the smooth muscle cell
not fully establishes until 7 months. At 6 months dilator muscle [radial]- Basal extensions
of anterior or pigmented epithelial layer. It develops even after birth. Never fully
independent of the epithelium.
 
Posterior iris epithelium.
 During development largely amelanotic.

 Continue with non-pigmented epithelium of CB.

 Intracytoplasmic melanin increases in 4th month, near pupillary margin

 7-8 month heavily pigmented.

 
Iris innervation.
Adrenergic and Cholinergic – not established until late in development. Full pigmentation
and the pattern of anterior surface not complete until a few years of postpartum.
Malformations.
Aniridia.
  Rare

 Autosomal dominant.

 Bilateral

 Absence of iris.

 Stump of hypercellular stroma with abnormal proliferation of pigment epithelium.

 Malformation or hypoplasia of outflow system.

 Anterior and posterior cortical lens opacities.

 Ectopia lentis.

 Hypoplastic optic nerve.

 Deletion of short arm of chromosome 11. [11p]

 Gene of nephroblastoma.

 AGR. Aniridia- G.U abnormalities- mental retardation.

 Anridia keratopathy.

Ciliary body.
The Ciliary body is derived from neuroectoderm and mesenchyme. It commences in 11 –
12th week with indentation of the outer pigmented layer of neuroectoderm by small
capillaries in the inner vascular mesenchyme. The Ciliary epithelium is formed from the
anterior edge of the optic cup but doesn’t differentiate like the rest of the retina,
approximately 3 months of gestation. Initially, the inner nonpigmented ciliary epithelium
is flat, but as the vascular sprouts enlarge they push inwards to form primitive radial
folds. This epithelium is thrown into folds, forming the ciliary process, and from fourth to
sixth differentiation occurs to produce tight junctions and interdigitations. Between 14
and 22 weeks 70-75 radial folds increase in height and complexity. The Ciliary
epithelium commences aqueous production as early as 20 weeks. The ciliary stroma is
formed from the mesenchyme lying between the optic cup and cornea, with primitive
muscle being visible at 3 months. Circular or radial muscle fibers donot differentiate until
much later in development and indeed are not fully formed until about 1 year of age.
During the fourth month a primitive scleral spur appears which is not fully formed until
after the first year of life.
Choroid.
The choroid develops early from the differentiation of loose mesenchyme that
surrounding the optic cup. Choroidal development is dependent on the vascular
framework that develops around the long and short posterior ciliary arteries. A palisade
layer of vessels that lie external to RPE forms the basis for the future choriocapillaries. A
second layer at 4 months extends to future choriocapillaries to form rudimentary vortex
veins. During 5th month an intermediate layers forms future sattler’s layer. The
condensation of neural crest cells around the anterior margin of the optic stalk forms cells
of choroidal stroma. Melanoblasts from the neural crest invade the Choroidal
mesenchyme during the seventh month, mature and form melanocytes.
 Differentiation of choriocapillaries begins simultaneously with that of the retinal pigment
epithelium during the fourth and fifth week of gestation.

 Diaphragmed fenestration, characteristic of the choriocapillaries, are first recognized after 7 th week
of gestation and more numerous during the ninth week.

 Pericytes are detected as early as the sixth week of gestation.

 By the end of second month, arteriolar channels [branches of the future short posterior ciliary
arteries] can be distinguished by their narrow lumen and walls of two or more cells.

 During the 3rd or 4th months definitive layering of the choroidal vasculature becomes apparent with
the development of the outer [sclerad], large vessel layer [of Haller].

 During the 4th month the long ciliary arteries form the major arterial circle.

 By the 5th month recurrent branches from the major arterial circle extends into the ciliary body.

 Final anastomosis with the arterial circulation of the choroid is not established until 8 th month of
gestation.

 Choroidal stroma begins the second trimester and by the end of the third month it is demarcated by
the sclera.

 Elastic tissue in stroma is first seen 4th month.

a. lids.

Sclera.
Scleral is developed from the mesenchymal cells around the optic cup. These cells are
neurocrest in origin. At 6 weeks development proceeds in a posterior direction. Sclera
also develops from inside outward. By the middle of the 7th week demarcation of sclera
from the surrounding tissues is apparent. At 9th week of gestation deposits of collagen is
recognizable. By 11th week cells almost attained adult appearance and at the same time
lamina cribrosa forms. At the beginning of 4th month, the sclera in both pre-and post
equatorial regions consists of 30 cell layers, this increases to 50 layers by the 6th month,
after which time no further mitoses are seen. At approximately 4 months [70mm] the
inner aspect of the anterior sclera develops a fibrous wedge-shaped protrusion the sclera
spur. By 5 months the sclera is fully formed. By the middle of the 7th month the anterior
ends of the longitudinal ciliary fibers have established their insertion into the sclera spur.
The deep and intrascleral vascular plexus, the aqueous veins and the collector channels
that traverse the sclera are first recognizable at about 12 weeks.
 
 
Development of Vitreous.
 
The development of vitreous is associated with the development of hyaloid artery.
At 4 weeks [5-7mm] stage, mesodermal cells invade the cavity of the developing optic
cup through the patent optic fissure. These cells differentiate into hyaloid artery and vasa
hyaloidae propia.
Primary vitreous.
Between 4th and 5th week [13 mm stage], the primary vitreous occupies the letrolental
space with fibrilar material, mesenchymal cells, and vascular channels. The fibrilar
material is ectodermal in origin. The mesenchymal cells differentiate the fibroblasts and
mononuclear phagocytes from the hyaloid artery. The primary vitreous attains the
maximum formation by 2 months gestation. By 5th month [16-mm stage] hyaloid artery
forms the capillary network to join the fibrilar capsule on the posterior surface of the lens.
Secondary vitreous.
The secondary is avasular and starts developing at 13-mm stage, continuos until the 70-
mm stage. It consists of type 2 collagen fibers and it occupies between retina and primary
vitreous.
Tertiary vitreous.
This other wise called embryonic zone of origin or vitreous base. It develops at 12weeks
[65mm] from the condensation of thicker collagen fibers of the secondary vitreous.
Tunica vasculosa lentis.
At 9th month [35mm] vascular vessels grow from the rim of the optic cup toward the
equator and anterior surface of the lens. They organized as capsulopupillay vessels. The
tunica vasculosa lentis reaches its greatest development at 40mm stage. By 4th month
atrophy of the hyaloid artery and simultaneous retraction of the primary vitreous occurs.
They confined to retrolental space. This area remains throughout life as cloquet’s canal.
Final organization of the vitreous.
At 5th month [160mm] the pupillary membrane and the posterior vascular capsule on the
anterior and posterior surfaces of the lens regress. At 7th month blood flow in the hyaloid
artery ceases and completely atrophied by birth. The phagocytes in the cortex of the
vitreous begin to synthesize hyaluronic acid.
 Surface ectodermal derived elements also contribute.

 Primary vitreous is mixed - ectodermal + mesenchymal origin.

 Secondary vitreous is avascular.

 Mesenchymal cell in adventia of vitreous vessels – vitreous matrix.

 After birth- much of hyaluronic acid and collagen [type 2] added.

  Tertiary vitreous. - Fibers firmly attached in developing pars plana region – when they mature
they form vitreous base.

 Non-pigmented epithelium of ciliary body are responsible for tertiary vitreous + Zonular fibers.

 Macrophages scavengers role in regression of Hyaloid vessels.

 
Malformations.
 Regression of Hyaloid system doesn’t occur.

 Dense vascularized collagenous tissue contracts and deforms.

 Persistence of tunica vasculosa lentis or pupillay membrane.

 Persistence of hyperplastic primary vitreous.

 Ciliary processes are drawn internally.

 Persistence hyperplastic primary vitreous.

 Persistence Hyaloid artery.

 Condensed posterior primary vitreous.

 Distortion of the disc and retina.

 Prepapillary and preretinal fibrous membrane.

 Radial or falciform folds in the retina.

Chamber angle.
 
The space between the first wave of mesenchyme and second wave of mesenchyme
forms a slit, which is future anterior chamber. At 7weeks [22-24mm], the angle lies in the
loosely arranged mesenchyme which form the future trabecular meshwork. By 15th week
the demarcation of the anterior chamber is present. By the 5th month, the anterior chamber
is rounded and it persists upto 7th month. The angle starts progress deepening at 3rd month
and continues upto the age of 4 years. By 7th month the deepest part of the angle has
receded to the level of Schlemn’s canal and by birth it is at the level of scleral spur.
The trabecular meshwork appears as the triangular or wedge shaped structure at 4
months. It consists of undifferentiated mesenchymal cells, which is neural crest origin.
These mesenchymal cells form the trabecular meshwork. By 4th and 8th months the cells
elongate and continue to secrete collagen fibrils, elastic tissue, and basal lamina material.
After the development of scleral spur at 22nd and 24th week, the meshwork is oriented to
longitudinal outer portion and net like arrangement of inner uveal meshwork. By 9th
month the uveal trabeculae are well formed.
The Schlemn’s canal develops from a small plexus of venous cannaliculi by the end of
the third month of gestation. During the 4th month the canal is surrounded by other
mesenchymal cells that secrete, and are enmeshed in basal lamina-like material and foci
of collagen fibrils. Eventually this forms the juxtacanalicular region. At about beginning
of the 5th month characteristic vacuolar configuration begin to appear in the endothelial
cells lining Schlemns’ canal. Upto 6 months of gestation both Schlemn’s canal and the
scleral spur are located posterior to the deepest part of the angle, but by 7 months the
angle reached to the level of the canal. Ultimately the canal comes to lie at the apex of the
angle.
 

Pituitary gland.
 
The pituitary gland is derived from the ectoderm [Rathke’s pouch] and the infundibulum
[part of the dienchephalon]. Rathke’s pouch forms the adenohypophysis [anterior lobe]
and pars intermedia. The infundibulum forms the neurohypophysis [posterior lobe] and
pituitary stalk, into which the infundibular recess extends for a variable distance.
Enlarging pituitary tumors, with the exceptions of craniopharyngioma, initially compress
inferonasal chiasmal fibers.
Development of face.
 

The face including the orbit begins its development in the 4th week of gestation and is
completed by 10th week. The orbit is formed from fusion between the lateral nasal
process and the maxillary process.
 Paired maxillary and mandibular process plus an unpaired frontonasal process.

Development of orbit.
 
The nasal process forms the ethmoid and lacrimal bones. The maxillary process
contributes to the floor and lateral wall of the orbit. All bones of orbit are membranous
except the lesser wing of sphenoid, which is initially cartilaginous. All bones ossify in the
3rd month. Fusion of bones takes place in 6th and 7th months. The adult dimensions of
bone not reached until adolescence.
 The first bone to be laid is the ethmoid at 6-8 weeks.

 The trochlea begins to consolidate at about 9 weeks.

Development of nasolacrimal duct.

The nasolacrimal groove forms along the fusion between the lateral nasal swelling and
the maxillary process. At [10mm] the ectoderm in the groove invaginates to form
nasolacrimal duct. Canalization of the solid columns of cells commences first in the
vicinity of the lacrimal sac. [3 months]. Mesenchyme condenses and ossifies around this
cord to form the bony wall of the nasolacrimal duct.
A full term infant eye is smaller, at = 14-16 mm, than an adult and has more refractive
media [especilly the lens] to prevent excessive hypermetropia. Iris pigmentation
commences a few days after birth and the infant corneal angle is narrower than that of
adults. Infant posses a small pupil, and medial rectus inserts adjacent to the limbus.

By Dr Allen

Chronological sequence in the formation of embryonic eye

from 2 weeks to 16weeks (4 months)

embryonic tissues involved:

2. surface ectoderm lens plate lens vesicle lens, corneal epithelium

and
endothelium, conjunctiva and skin of eyelids, lacrimal and
accessory
glands, drainage system, vitreous also partly formed by
mesoderm.

2. neural ectoderm bud optic stalk & optic vesicle

simultaneous invagination of optic stalk and optic
vesicle:
optic stalk choroidal fissure its fusion choroidal
tube
for hyloid artery
and after 16 weeks for central retinal artery and vein
optic vesicle optic cup approximation of
inner and outer cell walls
outer wall of optic cup becomes a single layer pigmented
epithelium of
retina, epithelium of the ciliary body, ciliary
processes, iris and sphincter and dilator pupillae
inner wall of optic cup undergoes differentiation to form 1. the
outermost layer, rods and cones, 2. the inner layer of bipolar cells
and
3. innermost layer of ganglion cells, and their respective nerve
fibres.
Macular development is not complete until 6 months after birth.

4. mesoderm forms i sclera

 ii stroma of cornea, conjunctiva, iris, ciliary body,
iii extraocular muscles, eyelids, hyloid artery, sheaths of optic
nerve
iv choroid
v connective tissue
vi blood supply of eye
vii bony orbit
viii vitreous
ix anterior chamber

4. endoderm does not contribute to the formation of the eye

Development of the eye takes place at the anterior end of the neural tube. The optic
vesicle is attached by optic stalk on either side to the forebrain. The neural tube lies in
the mesoderm.

2.5mm or 2 week stage : neural groove

4 mm or 3 week stage : fusion of neural groove, separation from surface ectoderm,

budding of neural ectoderm to form the optic stalk and optic vesicle. Thickening of the
surface ectoderm to form the lens plate opposite the optic vesicle. Simultaneous
invagination of optic stalk and optic vesicle to become choroidal fissure and optic cup
respectively.

9 mm or 4 week stage : lens plate separates from the surface ectoderm to form lens
vesicle
to lie free in the rim of the optic cup. Mesoderm forms a network of capillaries encircling
the optic cup to become the choroid by 6 weeks.

10 mm or 5 week stage : pigmentation of the outer wall cells of the optic cup to form a
single layer of pigment epithelium and Bruch’s membrane
differentiation of the inner wall cells into 3 other types of functional cells and their
respective nerve fibres of the retina.

13 mm or 6 week stage : choroidal fissure closed. Posterior lens cells grow forward.
Eyelid
develops from mesoderm except its skin and conjunctiva.

26 mm or 7 week stage : the axons of the ganglion cells of the retina form the optic
nerve. Mesoderm between the lens and the surface ectoderm forms the anterior
chamber, Schlemm’s cannal, trabecular meshwork and vascular septa of the optic
nerve.
 50 mm or 12 week stage : the rim of the optic cup forms the epithelial lining of the iris,
ciliary body and ciliary processes. Mesoderm infiltrates into these structures to form the
stroma. Neural ectoderm forms sphincter and dilator pupillae.

100 mm or 16 weeks : general structure of eye formed

Further development consists of differentiation, more rapidly in the posterior than in
anterior segment in early gestation and then reverses later.