EMBRYOLOGY OF EYE

Nitin J Renge,

EYEBALL Cystic,near to roof & lateral wall,Albate

spheroid Diamensions~Diameters AP

24mm,Horizontal 23.5mm,Vertical 23mm,Circumferance 75mm,Volume 6.5ml,Weight 7 gm

Two poles~Anterior & Posterior Three

Equators~Geometric,Anatomical,Surgical Three Axes~Optical,Visual,Fixation Three Visual angle~Alpha,Gamma,Kappa.

Only Kappa can be measured Three coats~Outer fibrous,Mid

Vascular,Inner Nervous Two Segments~Anterior & Posterior Two Chambers~Anteror & Posterior

Introduction The eyeball and its related structures are derived from

following Four primordia ;1. Neuroectoderm~outgrowth from procencehalon ,optic

vesical 2. Surface Ectoderm~lens placode and surrounding

accessory ocular structures3. Mesodem~surrounding optic vesicle 4. Visceral mesodem of maxillary process Derived from germ layers Ectoderm(2st) Mesoderm(3rd) Endoderm(1nd) First evidence of primitive EYE during 3rd week(day 22)of

gestation,embryo~2mm length with 8 pairs of somites

Embryology and regularity factors In embryology various endogenic regulatory factors

controls cellular differentiation, proliferation, cell migration and inductive interaction for the specific organ development.

Three groups of regularity factors are identified1.Growth factors

2.Homeobox genes/ master genes

3.Neural crest cells fibroblast

growth factors(FGF)

transforming growth factors Bs

insulin like growth factors (IGF-I)

control subordinate genes in regulation

of patterns of anatomical

development(morphogenesis) eg. PAX6-

marks the location of lens, HOX ( HOX8.1 –

corneal epithelium,HOX7.1-

ciliarybody)

Transient population of pluripotent

cells, originated

from neuroectoderm which latter

transforms into

mesenchymal cell

PAX6~Key regulatory gene for EYE developmentprechordal plate~circular localized area of columnar endodermal cells,future site of mouth

FGF,CHX10~regulate neural (inner) retinaTGF-B,MITF~regulate pigmented (outer) retinaPAX6,SOX2,LMAF,PROX1-responsible for lens crystallinSIX3~act by inhibiting crystallin geneBMP-4~secreted by optic vesicle,upregulate SOX2,LMAF

GASTRULATION-early 3rd week formation of three germinal layers Begins with primitive streak by 15th

day Primitive streak~visible as a narrow

groove with slightly bulging regions on either side in median plane caudally on dorsal aspect of embryonic disc with slightly elevated area on cephalic end,primitive node.

Epiblast cell migrates to primitive streak,become flask shaped and detach,migrate below epiblast

That replace hypoblat form endoderm and then form mesoderm.Remaining epiblast form ectoderm

GASTRULATION-beginning 3rd week

Primitive streak

Gastrulation-eaqrly 3rd week

Bilaminar embryonic disc with Migrating epiblastic

cellsGastrula with three

germ layers

Neuraltion and neural tube formation Neural tube is an important primitive

structure from which ocular primordia-the optic vesicle, the progenitor mesenchymal cell (from neural crest) and neural tissue develops

Begins as notochord develops,it induces overlying embryonic ectoderm in midline to thickened forming Neural plate(16 day of gestation) and that ectodem called neuroectodem

Neural plate form Neural groove on 18 day of fertilization and elevation of two side of neural groove forms neural fold,adjacent neural plate part form neural crest and ultimately fold fuses to become neural tube(22 day) and neural crest cells

Neuraltion and neural tube formation-22th day Neural

crest cell

Gartrula Neural grove

Neuraltion and neural tube formation-22th day

1.Neural plate

2.Neural

groove

3.Neural tube Neural crest cell-

proginater cells for mesenchymal

cells

Surface ectoderm

Formation of eye primordia-3rd week Primitive eye starts in 3rd week of gestation

when anterior portion of neural tube is folding

As the neural tube is folding 3 dilatation appears at the anterior portion of neural tube-forebrain (procencehalon), midbrain and hindbrain

Primitive eye originates as Optic primordia,thickening area on either side of midline on neural plate that destined to form procencehalon (venterolateral region of primitive forebrain)

Formation of optic and lens vesicle Begins with the optic primordia that

depressed to form optic sulcus then wall of optic sulcus deepens and wall of procencephalon overlying sulcus bulge to form Optic vesicle,proximal part become constricted and elongated to form optic stalk

With the formation of optic vesicle(25th day of gestation) it induce surface ectodermal cells,in contact laterally,thicken to form Lens Placode at 27 day of gestation(embryo 4-4.5mm)

Lens Placode convert into Lens Vesicle Lens Vesicle seprate from surface ectoderm

at 33 day of gestation

By end of 3rd week gestation Three primordial structure

are formed:

1. Lens placode

2. Optic vesicle

3. Mesoderm surrounding the optic vesicles

Optic cup formation

During Fourth week(embryo-7.6-7.8mm) of gestation Optic Vesicle converted to Optic cup by differential growth of wall of Optic Vesicle

Margin of Optic cup grow over lens vesicle from upper and lateral side but such growth doesn’t occur from inferior side forming Choroidal or Embryonic fissure

Choroidal Fissure closes by 6th -7th week of gestation,when fails Typical Colobomata result

By 7th week of gestation,most basic structure of eye are present

Concept of congenital anomalies Developmental anomalies Occurs due to

disturbance in embryonic events by various factors in 1st -3rd months of pregnancy, ocular structures are most at risk in the period of organogenesis from 18 – 60 days

1. Intrinsic factors 2.extrinsic factors(teratogen)Altered, defective or imperfective genes

Impaired cellular induction/proliferationDefective cell migration

Inadequate differentiation & cell death

Infection (Rubella, syphilis, cytomegalovirus, herpes simplex virus )radiation

Maternal diseases(eg.Diabetes)

Drugs/toxins-alcohol,thalidomide,antiseizure,retinoic acid ets

Anterior segments-developmentinclude crystalline lens suspended by zonules and structure anterior to it

Development of eye structure are mostly induced with the formation of optic vesicle and lens placode

Formation of lens Derived from surface ectoderm

With the formation of optic vesicle the surface ectoderm in contact with optic vesicle thicken and forms lens plate/lens placode-27th day

Eventually the lens plate invaginates and separates from surface ectoderm and forms lens vesicle -33rd day

Lens vesicle Lens vesicle has anterior wall with

cuboidal epithelial cell and posterior columnar epithelial cellsSynthesize type 1v

collagen & gylcosaminoglycans to

form lens capsule, maintains homeostatic

fuction of cell and equatorial cell serves

as progenitors for 2ndary lens fibers layed

concentrically throught lifeForms primary lens

fiber filled with protein crystalline - embryonic

nucleus

Cells of posterior wall lengthens and form elongated fiber that projects into the lumen and specific lens protein(crystalline) are synthesized make them transparent,nuclei disappears

Posterior cell contributes for most of the growth of lens for first 3 month-preserved as compact zone of lens, embryonic nucleus.

From 3rd month the anterior progenitor cells proliferates and produce 2ndary lens fibers also called fetal nucleus upto 8th month of gestation

In 3rd month inner most fibres mature with increase in cytoplasmic fibrillar materials and the cell nuclei and organelles decreases

Secondary fibers are displaced inward between the capsule and embryonic nucleus and meets on vertical planes to form Y shape suture anteriorly and inverted Y posteriorly & complicated dendritic pattern is observed in infantile and adult nucleus as growth of lens fiber assymetric following birth

Lens ~8.8-9.2 mm diameter At birth it weighs 65mg (adult at 80 yr-

258mg) with thickness of 3.5mm ( adult-5mm)

Lens fiber are formed throughout the human life developing into different layers of lens fibers

Lens anomalies !1.Congenital aphakia-absence of lens at birth

primary aphakia Secondary aphakia(more common)

Occurs due to failure of tissue migration from

surface ectoderm

Occurs due to spontaneous absorption

of developing lens

2.Lenticonus and lentiglobus- localised cone shape or spherical

deformity of lens surface Associated with Alports

syndrome-X-linked disease(lenticonus anterior)

characterized by defective genes for production of type 1V

collagen

Lens anomalies

Limited to either Embryonic or Foetal Nucleus Most are Idiopathic Herediatery-AD(most common),AR,X linked

Genetic a & metabolic disorders-Down syn, marfans syndrome,galactosaemia etc.

Maternal infection and toxicity- rubella(during 1st trimester), CMV, varicella, radiation,steroids, thalidomide , toxoplasmosis etc.

Lamellar (zonular) Cataract~most common, 50%,Involve Foetal Nucleus.

4.Congenital cataract-etiology

3.Lens coloboma- flattening/notching(lower quadrant of

equator) of lens due to absence of zonular fibers, associated with defect in iris, optic nerve/ retina as a result of abnormal closure of embryonic

fissure

Cotn…. Congenital Ectopic Lentis~displace lens

from normal position(patellar fossa)A. Simple ectopic lentis-

Bilateral,symmetric,upwards AD inheritance

B. Ectopic lentis et pupillaeC. Ectopic lentis with systemic anomalies Marfan’s Syndrome-AD,displace upward

and temp Homocystinuria-lens subluxated downward

and nasally Microspherohakia~lens spherical & small in

size, occur isolated or feature of syndrome e.g.Weil-Marchesani Syndrome or Marfan syndrome

Development of cornea-begin at 40th day of gestation & by 5-6th month atain almost adult app Development of cornea is

induced by lens and optic vesicle formation

With the separation lens vesicle the surface ectodermal cell proliferates to form epithelium of cornea

Basal lamina of epithelium cells secrets collegen fibers and gycosaminoglycans to form primary stromaCorneal

epithelium

Lens vesicle

Surface ectoderm

Corneal embryogenesis-5th week By early 5th week gestation

there are 3 waves of mesenchymal cells(Neural crest derived) migrating towards the corneal epithelium.

1st mesenchymal wave forms the corneal & Trabecular endothelium .

Desment’s membrane is derived from the basal lamina of endothelium

Corneal Nerve present by 5th month of gestation

Foetal Cornea very Hydrated compare to Adult So translucent rather than transparent

Ctn… 2nd mesenchymal wave

migrates between epithelium and endothelium and forms keratocytes or fibroblast

The keratocytes synthesis type 1 collagen fibers and proteoglycans(matrix) which are organized as lamellae to form stroma of cornea

Bowman’s layer~condensation of superficial accellular part of stroma(after 4th month & fully develop at birth)

Corneal derivatives Diameter at birth –10 mm( 9.5-

10.5mm)reaches adult size 12 mm by 2 years

Derived from surface ectoderm

Derived from mesenchyme(neur

al crest cell)

Derived from mesenchyme(neur

al crest cell)

Developmental anomalies-cornea

Due to fetal arrest of corneal growth in 5th month or related to the overgrowth of anterior tips of optic cup which leaves less space for cornea to develop

Inherits as autosomal dominant/recessive trait

Due to failure of optic cup to grow leaving large space for cornea to fill

Associated with abnormal collagen production-Marfan syndrome

Inherits as X-linked recessive pattern

1.Microcornea:Corneal horizontal diameter is less than

10mm since birth

2.MegalocorneaCorneal diameter more tha 12mm at birth or

more than 13mm after 2 years

Disorder of 2nd wave mesenchymal migration 90% bilateral & cornea whole or sometimes

only periheral cornea affected Sporadic but both autosomal dominant and

recessive inheritance pattern are reported

Endothelial dystrophy-Primary dysfunction of 1st mesenchymal wave/corneal endothelial cell degeneration. Autosomal recessive>dominant.

Stromal dystrophy –dysfunction of corneal stroma causing corneal opacity.

Causes of Congenital Cloudy Cornea~Sclerocornea,tear in descement membrane,ulcer,metabolic conditions (STUMED)

3.Sclerocornea-Sclera like clouding of cornea with ill-defined

limbus. Difficult to differentiate cornea and sclera

4.Corneal DystrophyDiffuse,ill defined flaky/featheary/blue-gray ground glass opacification of cornea. Cornea

is clearer peripherally

Corneal thinning and bulging due stromal and epithelium thinning, fragmentation of Bowman’s layer and folds or break in Descement’s membrane

Etiology unknown, usually multifactorial associated with Down syndrome, mental retardation and atopic diseases

Non inflammatory,Bilateral 85%,usually start at puberty & progress slowly

Defective Synthesis of Mucopolysaccharide & collagen tissue

5.keratoconus-Condition in which central cornea assume a conical

shape

Anterior chamber and angle formation By beginning of 3rd week there are three

successive in growth of mezenchymal cell surrounding the optic cup

1st wave of mezenchye forms corneal endothelium &Trabecular endothelium, 2nd waves forms Corneal stroma & Pupillary membrane & 3rd wave forms Iris stroma

Anterior chamber is first recognized as split like space between developing corneal endothelium and iris epithelium as a result of selective mezenchymal cell atrophy/cleavage

Anterior Chamber appears- 3rd Month of Gestation

Anterior chamber and angle formation ~anterior chamber depth determined genetically with Dominant Inheritance

1stMesenchymal wave form corneal

& Trabecular endothelium

2nd wave forms pupillary

membrane& Corneal stroma

3rd wave forms Iris Stroma

Primitive anterior

chamber-slitlike space

By 15th week of gestation corneal endothelial cells extend into the angle recess and meets with iris epithelium

By 3rd month angle recess deepens and forms iridocorneal angle

In 7th week – the angle of the anterior chamber is occupied by the mesenchymal cells of neural crest(1st wave) origin- forms trabecular meshwork

Schlemm canal develops from small plexus of venous canaliculi of endodermal origin and forms uveoscleral outflow/tract.

Schlemm canal appears in 4th month of Gestation

Completion of Ant.Chamber Angle formation~8th month of Gestation.

Trabecular meshwork The anterior chamber angle continuous to recede

until 6-12 month after birth when it become adult type appearance.

Anterior chamber depth is 2.3-2.7 mm at birth (adult-3mm range 2.5-4.4) In the final week gestation the

trabecular meshwork undergoes fenestration and communicates with anterior chamber

Congenital glaucoma may occur as a result of defect in terminal differentiation of trabecular tissue leading to excessive formation of meshwork collegen preventing formation of iridocorneal angle

Ciliary body and iris By 3rd week gestation there is

extension of 2 layers of neuroectoderm from the edge of optic cup

Its has outer pigmented epithelium(PE) and inner non pigmented epithelium(NPE)

Distal part of advancing neuroectoderm becomes an iris

Proximal part of neuroectoderm extension becomes the ciliary body

Ciliary body(CB)-ctn.. CB begins to appear at 9th week of

gestation Cellular proliferation of proximal 2

layers of neuroectoderm forms longitudinal indentation of outer pigmented epithelium

By 12 weeks Inner non pigmented layer forms radial fold(75) and become 70-75 ciliary processes(fully form in 4th month)

At 10 week mesenchymal cells get condensed at its anterior surface to form the stroma of ciliary body

At 12 weeks there is Myofillament proliferation of mesenchyme and forms smooth muscles of ciliary body by 5th month

Ciliary muscle continues to develop for at least 1year after birth.

Ciliary body By 4th month ciliary

body is functional and secrets aqueous humour which fills up anterior and posterior chamber

Ciliary epithelium synthesis collagen fibers which becomes suspensory ligament/zonules of lens

Zonules~Begin to develop at 10th week and by 5th month reach Lens

Development of iris-3rd month Developed from 2 layers; 1. Mesenchyme-anterior

stroma 2.Neuroectoderm of optic

cup– - iris pigment

epithelium -sphinchte and dilater

muscles

Iris begins to develop by condensation of 2nd wave mezenchymal to form Pupillary membrane

Iris epithelium-end of 3rd month Pupillary membrane formed

by condensation 2nd wave mesenchymal cell in early 3rd month

2 layers of neuroectoderm from the edge of optic cup extend to the posterior surface of pupillary membrane.

Three structures(PE,NPE and pupillary membrane) ultimately fuses to become an iris

Pupillary membrane

Iris- 3rd month

At 3rd month Cells of anterior epithelium layer differentiates into myofobrills and forms sphincter and dilator muscles of an iris

Pupillary Membrane(PM)-cells of PM differentiates into fibroblast like cell and secrets collegen fibrills & extracelluler matrix which is incorporated with PE to form the anterior stroma of an iris

Iris fully developed by 5th month pigmentation of posterior

epithelial cell occurs begins at the pupillary margin at midterm , by 7th month iris is fully pigmented

Iris and pupil-8th month gestation Pupillary membrane

begins to degenerate at about 8th months of gestation

Opening in the central part of iris forms the pupil

Iris stroma and dilator muscle is still immature at birth-pupil appears miotic at birth

Dilator Pupillae poorly developed & doe not reach adult proportions untill about 5th year of age.

Iris anomalies

Can be Associated with syndromic presentation like trisomy 13, klinefelter,turner, CHARGE association(ocular coloboma,heart defects, choanal atresia, mental retardation, genitourinary and ear anomalies)

1.Hypoplasia/absence of an iris Inadequate inductive interactive between

optic cup, surface ectoderm and neural crest cell due to Defect in PAX6 genes

Occurs as sporadic or autosomal dominant 2.Persistant pupillary membrane Most common congenital iris anomalies Failure to atrophy pupillary membrane 3.Iris Coloboma Failure of embryonic fissure to close in 6th or

7th week of gestation Pupil appears like inverted tear drop usually at

the inferonasal quadrant Can be associated wit coloboma of choroid,

retina, ciliary body and optic nerve

Iris anomalies…

7.Conginatal mydriasisMalfoamation of iris sphincter muscleSphicter Muscle of the Pupil is fully differentiated by 6th month of gestation

4.polycoria -Accessory iris opening Associated with Axenfeld-Reiger Syndrome

( autosomal dominant disorder) due to mutation of PAX and FOXC1 gene

Present with ,malformation of face, teeth, skeletal system

5.Corectopia-Displacement of pupil Associated with sector iris hypoplasia or

colobomatous lession or lens subluxation(ectopia lentis et pupillae)

6.microcoria-congenital miosis Occurs due to malformation of dilator pupillae

muscle Can be associated with microcornea,lens

subluxation, iris atrophy and glaucoma

Posterior chamber

Develops as a slit in the mesenchyme posterior to the developing iris and anterior to the developing lens

Anterior and posterior communicates when the pupillary membrane disappears and the pupil is formed

Aqueous humor fills these two chamber

Embryogenesis-Posterior segment Retina Optic nerve Vitreous Choroid Sclera Vascular system

Retina-originates from Neuroectoderm Neurosensory retina- originates from the inner

layer ofneuroectodermal cell of optic cup

Retinal pigment epithelium- Originates from the outer

neuroectodermal cell of an optic cup

Neurosensory layer-1st month Anterior 1/5th – forms the

posterior surface of developing ciliary and iris

Posterior 4/5th forms the primordial sensory retina

Single layer epithelium with ext &int basement mem

Proliferates to forms two 2 distinct zones by 4th-5th week(35th day)

Outer 2/3rd –primitive nuclear zone has rows of nucleated cells which will forms neural cells-Outer primitive zone or Nuclear zone or germinal epi

Inner 1/3rd- Inner marginal zone has cells devoid of nucleus which will form nerve fiber layers

Neurosensory(NSR) retina NSR begins to develop from outer primitive

nuclear zone(PNZ) with 8-9 row of nuclei Mitotic Cellular proliferation of PNZ forms 2

distinctive layers by 6th-7th wks1. Outer neuroblastic layer(forms photoreceptors)

forms rods &cones,biolar cells &horizontal cells2. Inner neuroblastic layer(Ganglion cell layers)

forms ganglion cells,muller’s cell &amacrine cells3. Two neuroblastic layer are seperated by transient

nerve fiber layer of Chievitz which become inner plexiform layer by 10.5th week gestation

NSR formation…ctn… Differentiation of outer neuroblastic layers

occurs(ONL)by 10th-12th week & form Bipolar & Horizontal cells & photoreceptor cells (rods and cones)

Differentiation Inner neuroblastic layers and form ganglion cell layer &layer of amacrine &muller cells(first inner nuclear layer)

Axons from ganglion cell develops at 10th-12th week and form primitive nerve fiber layers

A new intermediate nuclear layer,inner nuclear layer identified by 4th month in posterior pole retina contains biolar &horizontal cells also

Thus differentiation of Retinal Layer starts during 6th week of gestation & by 5th&1/2 month of gestation all layer i.e 10 layer of adult Retina are recognizable

Cellular proliferation and melanogenesis of outer wall of optic cup begins by 6th week and forms retinal pigment epithelium(RPE)

Initially RPE is mitotically active pseudostratified columnar ciliated epithelium cilia disappear as melanogenesis commence & mitotic activity ceases by birth

Mature RPE~hexagonal shape,homogenous in size & simple Cuboidal eithelium

By 15 week gestation all cells types , synapses and intercellular junction of neurosensory retina are formed

Fovea is formed by thinning of ganglion and inner nucleated layer by 24 weeks (7th month) of gestation

Outer 4 layer of retina get nutrition from Choroidal vessels & Inner 6 layer from Central Retinal Artery

Some imp landmark in Retina Development Synaptogenesis~in Cone pedical occur at

app.4th month & in Rod sherules at app.5th month

Photoreceptor outer segment formation commence arround 5th month

Horizontal cell become distinguishable arround 5th month

Microglia (resident tissue microhages) invade retina via retinal vasculature by 4th month & subretinal space by 10th week onward

Terminal expansion of muller cells beneath inner limiting membrane mature arround 4.5 months

Macular area~begin to differentiate at 11th wk of gestation, development delayed upto 8th month of gestation ,differentiate upto 4th-6th month after birth.

Optic nerve Develops from optic

stalk(connection between optic vesicle and forebrain)

Initially optic stalk has two layers

1. Inner neuroectodermal cells layer

2. Outer undifferentiated neural crest cells layer

Optic nerve formationLate in 6th week, cells of inner layer of optic nerve degenerates and become vacuolatedNerve fibers (axons) from the ganglion cells migrates through the vacuolated space of optic stalkBy 33 weeks it establishes an adult type optic nerve of app.1.2 million of axons Few cells of inner layer differentiated into glial cell which forms lamina cribosa by 8th week.Myelination~begin from chiasma at 7th month,proceeds distally & reach Lamina Cribrosa just before birth and stop thereIn some cases myelination extend upto arround Optic disc ~Cong. Opaque nerve fibre

Outer neural crest cells differentiates into (1)pia, (2)arachnoid and (3)dura matter which form optic nerve sheath by 4th month

Cong anomalies of Retina & Optic nerve

1. Congenital Retinoschisis~x-linked recessive, associated with stellate pattern at fovea & occasional vitreous haemorrhage

2. Norries’s disease~x-linked recessive, retrolental mass with elongated ciliary rocesses with retinal detachment.Associated with mental retardation

3. Incontinentia pigmenti~ ass. with proliferative retinal vascular abnormalities,total retinal detachment,cataract,RPE changes

4. Familial exudative vitreoretinoathy5. Congenital retinal folds

6.Morning glory disc anomaly Appears as funnel shaped excavation of

the posterior fundus that incorporates the disc.

Occurs due to abnormal closure of embryonic fissure(EF)

Disc has central excavation surrounded by elevated rim of pink neuroglial tissue with vessel emerging radially as spokes in all directions

Sometimes remnant of sheath of hyloid vessel form Bermeister papilla

7.Coloboma of optic nerve. May occurs as a part of chorioretinal

coloboma or solitary abnormality d/t EF fail to close

Can be associated with systemic abnormalities-CHARGE association~coloboma,heart disease atresia choanae,retarded gwth,genital hyolasia,ear anomalies with or without deafness

3.

Formation of vitreous Develops between lens and optic cup Mostly derived from mesoderm with

minimal contribution from ectoderm Formation of vitreous occurs in three

stages ; ❶ Primary vitreous~ Mixed ectodermal & mesenchymal origin, develop between 3rd-9th wk of gestation ❷Secondary vitreous~Neuroectodermal in origin, begin to develop arround 9th wk ❸Tertiary vitreous ~Neuroectodermal in origin, develop during 4th month gestation

Primary vitreous-1st month of gestation Network of delicate

cytoplasmic process which occupy the space between lens vesicle and inner layer of optic cup

Surface ectodermal element surround lens during invagination thought to contribute primary vitreous so mixed origin

It is composed of fibrils (ectoderm) and mesenchymal cells(mesoderm) which constitutes primary vitreous

Supplied by hyaloid vessels and its branches so it is vascular

Secondary vitreous- 2nd month of gestation onward (arround 9th wk) By 2nd month the hyaloid system

regresses and primary vitreous cell differentiates into hyalocytes which synthesis type 2 collagen and hyaluronic acid which constitutes secondary vitreous

2nd vitreous is avascular gel like substances occupying the space between primary vitreous and retina

By 5th -6th month primary vitreous and Hyaloid vessels undergoes atrophy, regress from perihery to centre & regration stop at optic disk leaving central retinal artery

Atrophied hyaloid vessels become hyaloid cannal which remain throughout the life as Cloquet canal, from optic nerve head to posterior surface of lens.

Primary vitreous

Tertiary vitreous-4th month Developed from Neuroectoderm in the

ciliary region during 4th month of gestation Represented by Vitreous base & ciliary

zonules Collagen fibrils synthesized

by ciliary epithelium becomes more condensed and extends to the lens equator and become zonular fiber of lens which constitutes the tertiary vitreous

Primary & secondary vitreous remain in contact with posterior lens casule as hyaloidcasular ligaments

Persistent hyperplastic primary vitreous(PHPV) or persistent foetal vasculature(PFV)

Presents as leukocoria-white pupillary reflex

Its occurs due to failure of primary vitreous and hyaloid vessels to regress

Severity range from pupillary strands & mittendrof’s dot to dense retrolenticular membrane &/or retinal detachment

Two tyes 1)Anterior PFV 2)Posterior PFV

Prognosis of Posterior PFV is poor Insufficient level of Vitreous

Endostatin may be pathogenesis Normal retinal development

required for proper vitreous biosynthesis(some str. Component synthesized by Muller Cells)

Choroid Vascular endothelium and the haemopoietic

cells of choroid are derived from endoderm

Choroidal stroma ( vascular pericytes, smooth muscles, melanocytes and collagenous components) of choroid are derived from inner vascular layer of mesenchyme that surround optic cup(Neural Crest)

Choroid..cntn Differentiation of neural

crest cells form choroidal stroma by the end of 3rd month gestation

Endothelium line blood vessels appears in the choroid stroma and forms choriocapillary

By 4the week Choriocapillary begins to differentiate,6th wk completely form and by 2nd month it anastomosis with short ciliary artery

By 5th month all layers of Choroid now visible and melanocyte appear in it’s external portion

By 8th month final arterial circulation of choroid is established after anastomosis with vessels of ciliary body and iris

Sclera Sclera is mostly ectodermal (neural crest) in

origin, however posterior region are mesoderm in origin Sclera begins to develop by

condensation of mesenchymal cells around the anterior rim of optic cup

Mesenchymal cells proliferates and deposits glycosaminoglycans, collagen and elastin fibrils and forms stroma of sclera

Process Starts at Limbal Equatorial region (future site of extraocular muscle insertion) arround 7th wk of gestation

By 5th month sclera is relatively well or complete formed

Vascular system of eye

Arterial wall has three layers;

1. Tunica adventitia(connective tissue)

2. Tunica media(smooth muscle layer)

3. Tunica intima( endothelium) Tunica adventitia and tunica media of ocular vessels are derived from neural crest cells(ectoderm)

Tunica intima is derived from endoderm

Primitive orbital vessels During early embryonic life untill 8th month, the

developing ocular structure is nourished by three transient vessels originating from internal carotid artery;

A. Ventral ophthalmic arteryB. Dorsal ophthalmic arteryF. Stapedial artery Ventral artery later atrophy and only a portion remain

as long posterior nasal ciliary artery

Dorsal ophthalmic artery become definitive ophthalmic artery

Stapedial artery becomes Middle meningeal artery

Primitive ocular vesselsEmbryonic intraocular vasculature system has two components;1. Anterior system- supplies anterior segment formed in iris and pupillary membrane formed by the branches of ophthalmic artery-

seven anterior ciliary artery and two long posterior ciliary artery

2.Posterior system- supplies posterior segment formed within the vitreous formed by hyaloid vascular system

Anterior artery system Anterior artery system is formed

by two long posterior,10-20 short ciliary artery and 7 anterior ciliary artery which are the branches of dorsal opthalmic artery

Anastomosis of long posterior ciliary arteries and anterior ciliary arteries forms major arterial circle at the root of iris

Vascular twigs from major arterial cicle and annular vessels forms the pupillary arcade

With the disappearance of pupillary membrane pupillary arcade remain peripherally as minor artery circle which supply iris

Posterior ciliary artery

Anterior ciliary artery

Posterior arterial system

Hyaloid artery nourishes the developing eye globe until the 8th month of gestation

Hyaloid artery is the branch of primitive dorsal ophthalmic artery emerges in 5th week of gestation

Later the Hyaloid artery regresses and become central retinal artery

Hyaloid system…. As the optic vesicle

develops there is incomplete folds in its inferior portion of cup and stalk called embryonic fissure

Embryonic fissure allows hyaloid system to be incorporated within the eye.

In 5th week Hyaloid artery enters the embryonic fissure of optic stalk.

With the fusion of fissure the hyaloid system are enclosed within the eye

Hyaloid system Branches of the hyaloid artery supplies

developing lens, vitreous, optic nerve Anastomosis of branches of hyaloid artery

forms 3 arterial arcades called Tunica vasculosa Lentis by 9th wk1.Anterior vascular

capsule2.Capsulopupillary portion3.Posterior vascular capsule

Valsa hyaloida propria(small capillary branches)

Hyaloid artery

Retinal circulation By 4th month the hyaloid artery bud of to

from central retinal artery Hyaloid artery system begin to atrophy and

regresses in 3rd month of gestation Retinal artery vascularizes the retina by

giving four branches two for temporal and two for nasal side, supplies inner six layer of retina

Nasal retina completes vascularization prior to temporal retina in 7th month of gestation

By 9th month all retinal part are vascularized except for portion of peripherals temporal retina

Retina also well developed nasal side before temporal

Retinal circulation Atrophied hyaloid

system

Retinal vessels buds from hyaloid artery and vascularizes retina

Vascularization reaches nasal ora serrata by 7th month and temporal periphery by 9th month

Retinopathy of prematurity

ROP associated with systemic abnomalities as anaemia,BPD,

cardiac defect,NE,IVH,cerebral palsy &neurodevelomental delay

Premature baby has incomplete vascularization of retina

Hyperoxia(supplementary oxygenation) causes vasoconstriction

Vasoconstriction causes ischemia in the incompletely developed retinal periphery

Ischemia trigger abnormal vessel formation called neovascularization- retinopathy of prematurity

ROP has five stages & VEGF has important role in pathogenesis

Accessory ocular structures EYELIDS~ start at 6th- 7th wk of IUL,margin of

two lids unite with flimsy tissueby 9th wk & separate 5th month of IUL(uto 26th-28th wk)

Both eyelid formed by reduplication of surface ectoderm

1.Lower eyelid-Formed from maxillary process & connective tissue & tarsal plate from visceral mesoderm of Maxillary process

2.Upper eyelid-Formed from lateral and medial aspect of frontonasal & connective tissue & tarsal late from periocular mesodem derived from neural crest

Skin of eyelids and it’s derivatives cilia,cojunctival & Tarsal Gland-from Ectodermal cell from lid margin.

Continue………. Conjunctiva~ from surface ectoderm Lacrimal apparatus~ 1.Lacrimal Gland-from 8 cuneiform eithelial

bud from superolateral side of conjunctival sac, by end of 2nd month.At term still undeveloped & tear not formed

2.Lacrimal Sac,Nasolacrimal duct and canaliculi-developed from ectoderm of nasolacrimal groove

Nsolacrimal duct becomes completely patent only after birth

Extraocular Muscles~are some of few periocular tissues that are not neural crest origin,differentiated from prechordal mesenchyme,start in 5th-6th wk (LR,SR,LPS-5th wk;SO,MR-6th wk & then IO,IR)

Conti….. Orbit~derived above from mesenchyme

encircles optic vesicle,below & laterally from maxillary processes,medially by frontonasal process & behind by pre-and orbitoshenoid.

Orbit Bone Formed by membraneous ossification

Bone differentiated during 3rd month Initially Optic Axis direct laterally, later

they directed anteriorly At Birth Orbit is hemispherical & more

divergent (50 degree) as compare to adult-45 degree

Eyeball reaches Adult Size by 3 year of age Orbit alteration in shape & grows until Puberty

Congenital anomalies of Eyelids1. Eicanthal fold2. Telecanthus 3. Epibleharon 4. Blepharophimosis 5. Eurybleharon 6. Coloboma of lid~Upper lid at middle &

lateral third seen in Goldhar’s Syndrome, Lower lid seen in Teacher collins Syndrome with hypolasia of lower lid

7. Ankylobleharon8. Cryptophthalmos~failure of sepration of lid

during 4th to 6th wk of IULthus lids fail to develop & skin passes from eyeball to cheek hiding eyeball

Congenital anamolies of conjunctiva1. Congenital cystic lesions~ rare,include

congenital corneoscleral cyst & cystic form of epibulbar dermoid

2. Dermoid ~common congenital tumour,occur at limbus,solid white masses,firmly fix to cornea

3. Lipodemoid (epibulbar dermoid)~at limbus 0r outer canthus,movable subconjuntival mass

4. Naevi or Congenital moles~common pigmented lesions,mostly near limbus,appears in early childhood & may increase in size at puberty or during pregnancy

Congenital anomalies of lacrimal apparatus1. Congenital NLD block~in 80-90% residual

membrane spontaneously dissolve within 2-4 month after birth

2. Congenital lacrimal Fistula (lacrimal anlage duct)~ fistula open on skin below and medial to lower punctum , may associated with congenital NLD block

3. Punctal Atresia~Imperforated punctum, presumed location of punctum

identified as a shallow dimple at appropriate site

Human eye at birth and after birth Newborn are hypermetropic by 2-3D

because of less axial length of eye( at birth 16.5mm, adult 24mm,70% of adult attained by 7-8 years)

Corneal diameter is 10mm at birth and 11.7mm in adults is attained by 2 years of age

Radius of corneal curvature is 6.6-7.4 mm at birth and 7.4-8.4 in adults

Retina fully differentiated at birth except Macula, differentiate in first 4 month with foveal reflex

General picture of fundus as adult after 6th month

…………continue Newborn has miotic pupil because dilator

pipillae muscle is not well form at birth.Reach adult proportion~at approximately 5th year age

Lens Spherical at birth Orbit is more divergent (50) as compared to

adult (45) Anterior chamber is shallow and angle is

narrow Visual development Pupillary light reflux-present after 31 week of gestation Blink reflex to light- several days after birth 6 weeks-maintain eye contact and react with facial

expression 2-3months –preferential to bright objects Conjugate fixation~become established by 6th month

References

1.Anatomy and Physiology of eye-2nd edition,Dr.A K Khurana

2.Ophthalmology,third edition,Dr.A K Khurana

3.Langman’s Medical Embryology,11th edition

4.Parsons Diseases of eye,22nd edition5.Yanhoff’s Ophthalmology,4th edition6.Essential of Embryology and Birth

Defect,7th edition7.Internate Resources

Thank you