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Embryology of eye

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  • Ectopia¤ Displaced pupil• Corectopia¤ Deformed pupil

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  • 1. Embryology of Eye Varun Shrestha First Year Resident Nepal Eye Hospital 2013
  • 2. Importance • To understand the structure of normal adult eye and its anatomic characteristics • the pathogenesis of numerous congenital anomalies of the eye that may occur as a result of defective embryogenesis • The various diseases of the eye
  • 3. 3 elements have been identified that regulate: • Growth Factors  Fibroblast growth factors (FGF)  Transforming Growth Factor- (TGF Insulin like Growth factor-I (IGF-I) and TGF- ) • Homeobox genes - DNA sequence found within genes that are involved in the regulation of patterns of anatomical development (morphogenesis)  PAX 6  HOX (HOX8.1, HOX 7.1) • Neural crest cells
  • 4. Synergistic action of these multiple trophic factors appears to be a significant regulatory tool for • Initiating cellular activities and • For limiting abnormal development
  • 5.  Neural plate Ectodermal cells of anterior portion of embryonic plate proliferates + thickens  Neural groove Medial longitudinal furrow  Neural fold Elevation at 2 sides of the neuroectoderm  Neural Tube neural folds meet at midline
  • 6. At the anterior portion of the neural tube 3 dilatations are formed
  • 7. The eye begins to develop as a pair of optic vesicles on each side of the forebrain Of the three germ layers of the embryo, only two are involved in the development of eye • Ectoderm – surface ectoderm neuroectoderm • Mesoderm
  • 8. EMBRYOGENESIS OF EYE • PRIMITIVE EYE  starts in 3rd week of gestation when anterior portion of neural tube is closing. • It origins as optic pit thickening on either side of midline in the ventrolateral region of primitive forebrain
  • 9. • The optic pit enlarges to form 2 globular structures at either side Primary Optic Vesicles. • Which connects to the forebrain via a n Optic Stalk • Primary optic vesicle meets surface ectoderm
  • 10.  During 4th week of gestation optical vesicle invaginates distally and inferiorly  formation of two layered optic cup  Optic cup is widely open distally and inferiorly.  Invagination also involves the optic stalk so this inferior groove forms Optic fissure/ embryonic fissure
  • 11. Invagination of optic vesicle Rim of optic cup Lateral wall of Forebrain Embryonic fissure
  • 12. Embryonic fissure  Closes at 6th week  Closure begins at centre and extends anteriorly and posteriorly until only a small crescent remains open at the posterior pole.  IMPORTANCE: Through the fissure there is  Outgrowth of axons from ganglion cells which form the optic nerve  Ingrowth of vascular elements which aids in growth and development of the eye
  • 13. Applied anatomy • Failure of fusion of this fissure -6th/7th week results in coloboma formation Anterior extreme  Colobomas of iris Posterior extreme  Colobomas of posterior fundus and optic nerve • Anterior and posterior aspects of cup are open for longer time hence it is exposed longer to teratogenic insults
  • 14. Coloboma iris Coloboma optic disc
  • 15. RETINA • Develop from two layers of optic cup  Sensory retina is formed by the Inner layer of optic cup  Retinal pigment epithelium is formed by the outer layer of optic cup
  • 16.  Retinal Pigment layer It is a single layer of columnar cells  initially it is non-pigmented but at 5th week melanogenesis begins (Premelanosomesmelanosomes Differentiation begins at posterior pole and proceeds anteriorly  Neurosensory layer The anterior 1/5th  forms posterior surface of developing ciliary body and iris The posterior 4/5th  initially divided intoinner marginal zone -devoid of nuclei outer primitive nuclear zone which has 9 rows of nuclei
  • 17.  Later the outer nuclear layer invades the inner marginal layer at the time of closure of embryonic fissure, so retinal Neurosensory cells divide into  Outer neuroblastic layer which contains horizontal, bipolar nerve cells, rod and cone cells  Inner neuroblastic layer which contains ganglion cells, amacrine cells, muller cells  These layers are separated by the Transient nerve fiber layer of Chievitz which later forms the inner plexiform layer  The inner 9 layers of retina are formed by merging of these two cell layers  By the 8th month of fetal life all layers of retina are recognizable
  • 18. • Ganglionic cells are the first cell of retina to be clearly differentiated • Cones outer segment form - month • Outer Rods segment form -7 month • photoreceptor cells continue to form after birth so it develops the ability for increasing resolution and sensitivity
  • 19. • Ora serrata – is a wavy line that lies between the small non nervous layer near the edge of cup large photosensitive portion in the inner layer of optic cup • Macula – has localized increase of superimposed nuclei in the ganglion cell layer, lateral to optic disc, in mid term • Fovea centralis – during 7th month, thinning of centre of macula due to peripheral displacement of ganglionic cells. Ganglionic layer Inner Nuclear layer Foveal Depression Outer plexiform layer/Henle’s layer *
  • 20. Applied Anatomy  Areas where RPE does not form(sometimes along the line of closure) the underlying choroid/sclera/neuroretina is hypoplastic.  Retinal detachment- Potential space between the inner and outer layers of optic cup is the site for retinal detachment.  Foveal region is extremely thin, devoid of ganglion cells and retains relative transparancy, allowing persistent transmission of underlying highly vascular choroidal hue eg. Cherry Red spot (Sphingolipidoses)  Juvenile Retinoschisis- splitting of the retina in the nerve fiber layer.
  • 21. OPTIC NERVE  Optic stalk and optic axons together form the optic nerve.  Its the constricted elongated area between primitive eye and forebrain  Initially there is an inner zone (neuroectodermal cells) and outer zone (undifferentiated neural crest)  th weeksome cells of inner region vacuolate+ degenerate+ remaining inner zone differentiates into glial cells.  Axons from ganglion cells run through the inner layer of stalk  Cells of inner layer encroach on the cavity of the stalk  cavity disappears  End of gestation Development of lamina cribrosa
  • 22.  Myelination of axons of optic nerve begins just before birth and continues some time after birth  Optic disc- the point where the axons from ganglionic layer of retina converge to leave the posterior surface of optic cup along with the optic stalk  Optic chiasma- partial decussation of the axons of the 2 optic nerve  Optic tracts  Lateral geniculate bodies  Tectum of midbrain
  • 23. • Applied anatomy: • Optic nerve – Aplasia – Hypoplasia • Morning Glory Syndrome - central excavation surrounded by an elevated rim of pink neuroglial tissue with the vessels emerging radially from the disc as spokes in all directions • Pit of the optic disc
  • 24. Lens • Begins development at 3rd week • Derived from surface ectoderm • Triggered by interaction of forward growth of optic vesicle with surface ectoderm thickens and forms lens placode • It invaginates to form lens pit that eventually seperates + meets at the margin lens vesicle
  • 25. CORNEAL EPITHELIUM ANTERIOR WALL- single layer of cuboidal epithelium POSTERIOR WALL- increases in length and form elongated fibres that projects into lumen of vesicle (crystallin) NUCLEAR BOW- nuclei of the lens fibers move anteriorly to form a convex line
  • 26. • Nuclei disappears. • Additional lens fibers are formed by mitotic division of the anterior epithelial cells at preequatorial region Secondary fibers • These are formed through out life. • Basal ends are attached to the basal lamina while apical ends extends to primary fibers As the fibers are laid down concentrically laminar appearance of the lens • New fibres are added concentrically around the old central fibres around the equator
  • 27. • Drawing shows formation of the lens vesicle and optic cup. The optic fissure is present because the optic cup is not fused inferiorly.
  • 28. Different layers seen in adult eye: • Embryonic nucleus- 1st to 3rd month of embryonic life (Primary fibers) • Fetal nucleus- 3rd to 8th month of fetal life • Infantile nucleus- last weeks of fetal life to puberty • Adult nucleus- formed after puberty • Cortex- recently formed fibers, beneath epithelium anteriorly, beneath capsule posteriorly
  • 29. • SUTURES  The linear juncture where the fibers terminate and abut each other. • Y Sutures- begin to form  2nd month  Anterior upright  Posterior inverted
  • 30. • Later in gestation and following birth sutures become complex and dendriform. • LENS CAPSULE  Vascular lens capsule formed from mesenchyme surrounding the lens, Disappears after birth  True lens capsule formed from Thickened basal lamina, which develops from lens epithelium.
  • 31. • The Zonular Apparatus begins to develop after the tertiary vitreous has formed. • Ciliary Epithelial cells synthesize collagen fibrils of the zonular fibers. • By 5th monthincrease in number, strength and merge with the anterior and posterior capsule.
  • 32. Applied Anatomy  Unequal growth of fibers from posterior wall + New fibers growing from equatorial regions  Elliptical shape of lens  Lens epithelial cells left behind in the capsular bag after ECCE  PCO (posterior capsular opacification) development. Clinically 2 types of PCO, fibrosis type proliferation and migration of lens epithelial cells, which undergo Epithelial-to-Mesenchymal Transition fibrous metaplasia producing folds and wrinkles in the posterior capsule. pearl typeremnants located at the equatorial lens region (lens bow) causes regeneration of crystallin expressing lenticular fibers and forms Elschnig pearls and Soemmering ring  If sutures are not formed and the fibers meet at a single point at anterior and posterior pole a pit would be formed poor optical properties
  • 33. CONGENITAL CATARACTS
  • 34. THE VITREOUS BODY Develops between the lens and optic cup • Primary vitreous– formation at 1st month Network of delicate cytoplasmic processes derived partly from lens and partly from retinal layer of optic cup and mesenchymal cells Supplied by hyaloid vessels and its branches • Secondary vitreous - formation at 2nd month Between primary vitreous and retina and is avascular Derived from retina and replaces the primary vitreous extracellular matrix composed of type II collagen+ hyaloctes Hyaloid vessels undergo atrophy – hyaloid canal (5th -6th mth-) cloquet’s canal which extends from optic nerve head and posterior surface of lens, Funnel shaped
  • 35. • Tertiary vitreous- at 4th month • Between ciliary processes and lens capsule • Large no. of collagen fibres develop with formation of zonular fibres
  • 36. • Applied anatomy • Mittendorf’s dot: remnants of anterior end of hyaloid artery associated with posterior polar cataract & attached to posterior lens capsule. • Subluxation/Ectopia lentis: Partial or total failure in Tertiary vitreous development • Bergmelster’s Papillae: flakes of glial tissue projecting from the optic disc • Persistent Primary hyperplastic vitreous: U/L, premature child.
  • 37. UVEA • • • • Middle vascular layer of eyeball Composed of iris, ciliary body choroid Stroma of all these are mesodermally derived Consists of blood vessels, pigmented cells called melanocytes and connective tissue.
  • 38. IRIS  Developed from 2 layers  Mesoderm – Anterior stroma  Neuroectoderm-  iris pigment epithelium  sphincter and dilator muscles  pupillary membrane is formed by condensation of mesenchyme situated in the anterior surface of the lens  2 layers of neuroectoderm forming the edge of optic cup extend to the posterior surface of pupillary membranethese structures fuse to become iris  Opening in the central part of iris becomes the pupil  Pupillary membrane begins to degenerate at about 8th months of gestation
  • 39.  Applied anatomy  Varying amount of atrophy of stromal vessels (pupillary membrane) while peripheral membrane remains well developed produce the fine architecture of iris crypts  Pigmentation of stroma doesn’t become evident until after birth, hence newborns usually have blue iris
  • 40. Polycoria, Ectopia, Corectopia, Aniridia
  • 41. CILIARY BODY AND SUSPENSORY LIGAMENTS OF LENS  Mesenchyme at edge of optic cup forms the Connective tissue of ciliary body,  Smooth muscle fibres of ciliary muscle,  suspensory ligaments of lens  2 epithelial layers formed from neuroectoderm at the edge of optic cup  outer pigmented  Inner devoid of pigment  Ciliary body is situated between future iris epithelium and peripheral retina  Ciliary epithelium undergoes folding to form 70-75 ciliary processes
  • 42.  CHOROID Middle vascular coat of eyeball. Begins to form at the anterior region of the cup & proceeds posteriorly. Formed from mesenchyme surrounding the optic vesicle Has layers. The innermost Bruch’s membrane is derived from basement membrane of RPE , choriocapillaries layer, Elastic tissue and collagen fibrils The outer layers layers are the - vascular and capillary During 5th month melanocytes of neural crest origin may be seen Melanocytes of neural crest origin are predisposed to development of malignant melanoma
  • 43. NUTSHELL:  Iris muscle-ectodermal in origin  Ciliary muscle is mesodermal in origin
  • 44. CORNEA Formation of cornea is induced by lens and optic vesicle formation  Epithelium derived from – surface ectoderm  Bowman’s membrane and Substantia propria – mesenchyme  Descemet’s membrane – endothelial cells  Endothelium – neural crest
  • 45. Keratoconus • Is a condition when the cornea assumes a conical shape secondary to stromal thinning
  • 46. SCLERA  Outer tough fibrous coat of eyeball  Originates as the condensation of mesenchyme outside the optic cup  7th week of gestation  First forms at the limbal region and progresses peripherally until posterior pole is reached 5th month  Primitive mesoderm differentiates into collagen and elastic fibres of an adult sclera
  • 47. ANOMALIES MICROCORNEA • Adult cornea<10mm in horizontal diameter • Related to fetal arrest of growth of cornea in 5th month MEGALOCORNEA • diameter 12mm or > at birth&13mm or>after 2 yrs • Due to failure of optic cup to grow &of its anterior tips to close
  • 48. Sclerocornea • There is ‘sclera-like’ clouding of cornea • Disorder of second wave mesenchyme migration • 90% bilateral
  • 49. ANTERIOR CHAMBER  It arises as a slit in the mesenchyme between the surface ectoderm and developing Iris.  th week angle of the anterior chamber is occupied by mesenchymal cells of neural crest originTrabecular meshwork  rd monthSchlemm’s canal develops from small plexus of venous canaliculi. The endothelial lining of Schlemm's canal is mesodermal in origin.  th monthVacuolation of the endothelium around Schlemm's canal occurs individual cells are connected by zonulae adherentes  Final differentiation of definitive filtration apparatus occurs shortly before birth.
  • 50. Schlemm canal Trabecular meshwork Scleral spur
  • 51. POSTERIOR CHAMBER • Split in the mesenchyme posterior to the developing iris and anterior to the developing lens. • Anterior and Posterior Chamber communicates when the pupillary membrane disappears and pupil is formed • Aqueous humor fills these two chambers
  • 52. VASCULATURE • At 5-6mm stage simple endothelial tubes bud from internal carotid artery grow towards developing optic cup • 2 Main vessels in this period  dorsal ophthalmic artery  ventral ophthalmic artery Invests the more medial portion of the cup & almost disappears except a portion of Long Posterior nasal ciliary artery(LPNCA) At 3rd week branches to form hyaloid artery which enters the embryonic fissure at 7-8mm stage Becomes definative dorsal opthalmic artery at th week Supplies the TLPCA, SPCA,CRA • The system drains into future cavernous sinuses by way of plexuses
  • 53. HYALOID VASCULAR SYSTEM Embryonic intraocular vasculature system is divided into 2 component  Anterior system  In the region of iris  Composed of pupillary membrane  Posterior retrolental system  within vitreous  composed of    hyaloid artery vasa hyaloidea propria tunica vasculosa lentis
  • 54. ANTERIOR SYSTEM  MAJOR ARTERIAL CIRCLE OF IRIS: anastomosis of the anterior ciliary arteries with the Long posterior ciliary arteries, near the root of the iris  PUPILLARY MEMBRANE: Radial vascular loops over the surface of the iris and lens+ formed by Annular vessel & major arterial circle.  MINOR ARTERIAL CIRCLE OF IRIS: Central portion of the pupillary arcades disappear but the peripheral remains as minor arcade.
  • 55. Applied Anatomy • Persistent pupillary membrane
  • 56. POSTERIOR SYSTEM  HYALOID ARTERY  Branches from the Dorsal ophthalmic artery- 3rd week- enters the optic cup via embryonic fissure  Grows anteriorly towards lens.  Supplies lens, vitreous and developing optic nerve.  By 4th month many branches bud off to form main branches of central retinal artery- the first permanent intraocular blood supply.  Continues to be an important source of nutrition till the beginning of 8th month of gestation.
  • 57.  VASA HYALOIDA PROPRIA  Small capillary branches that extend from main trunk of hyaloid artery through out vitreous  Anastomose with each others and with tunica vasculosa lentis
  • 58.  TUNICA VASCULOSA LENTIS  Formed by terminal branches of main trunk of hyaloid artery  2 branches  Anterior tunica vasculosa lentis  Posterior tunica vasculosa lentis  Extend around equator of lens to form lateral tunica vasculosa lentis/ capsulopupillary vessels  Anastomose with anterior tunica vasculosa lentis and makes a drainage system through annular vessels and later in gestation through ciliary vessels
  • 59. Long Posterior ciliary arteries Anterior vascular capsule capsulopupillary portion Posterior vascular capsule Hyaloid Artery Tunica Vasculosa Lentis
  • 60. HYALOID VASCULAR SYSTEM(cont..) • Begins regressing even before some of its components have not reached peak of development • Stimulus – unknown • 1st to regress  vasa hyaloida propria  tunica vasculosa lentis Finally main hyaloid artery
  • 61. RETINAL CIRCULATION • By 7th -8th month of gestation, retinal vessels would have extended nasally to ora serrata but only to equator temporally • Vessels reach ora on temporal region only close to term and even after birth • APPLIED ANATOMY: Retinopathy of prematurityexcessive O2 in premature infantsvasoconstrictionobliterated veinsneovascularizationvascular area is nonstretchable (detaches)/ non-vascular area is stretchable.
  • 62. UVEAL CIRCULATION  Develops from vasoformative paraxial mesoderm that surrounds the optic cup  6th wk-  Common temporal ciliary artery branch of dorsal ophthalmic artery runs along the temporal aspect of stalk & cup  Common Nasal ciliary artery branches of ventral ophthalmic artery runs along the nasal aspect of stalk & cup  These two vessels are the precursors of long posterior ciliary artery  These anastomose with each other posteriorly & anteriorly to form greater circle of iris
  • 63. • 3rd month 12 -15 short posterior ciliary arteries develop from dorsal ophthalmic artery Anterior ciliary artery Develops from small tributaries from muscular & lacrimal branch of ophthalmic artery Anastomose with branches of long posterior ciliary artery
  • 64.  Develop as folds of surface ectoderm above and below the developing cornea.  Folds fuse at 3rd month intrauterine life.  A closed space, conjunctival sac, exists in front of cornea.  Separation of eyelids starts by 5 month and completes by the 7th month. EYELIDS
  • 65.  Connective tissue and tarsal plates Mesenchymal core of the lids  Eyelashes epithelial buds from surface ectoderm  First appear in upper lid Arranged in 2-3 rows  Glands of Zeis and Moll ciliary follicles  Tarsal/Meibomian glands develop as columns of ectodermal cells from lid margins Gland of Zeis and Moll Mebomian gland Orbicularis Oculi Cornea
  • 66. APPLIED ANATOMY- EYELID • cryptophthalmos Failure of separation of eyelids – In cases of cryptophthalmos usually cornea is absent • Ankyloblepharon adhesion of eyelids • Epicanthal Foldspalpebralis, tarsalis, supraciliary and inversus
  • 67. EXTRAOCULAR MUSCLES • From the mesenchyme in the region of developing eyeball – four recti muscles superior and inferior oblique muscles • Initially represented as a single mass of mesenchyme • Later separates into distinct muscles, first at insertions and later at their origins
  • 68. • Levator palpabrae superioris formed last splitting from the mesenchyme that forms the superior rectus • During development, muscles become associated with IIIrd, IVth and VIth cranial nerves • Orbicularis oculi muscle• Mesenchyme of 2nd pharyngeal arch • Invades eyelids • Supplied by VIIth cranial nerve
  • 69. APPLIED ANATOMY OF EOM  During congenital ptosis there is paralysis of superior rectus muscle .
  • 70. LACRIMAL GLAND  Form as series of epithelial buds, which grow superolaterally from superior fornix of conjunctiva into the underlying mesenchyme  Buds canalize- secretary units multiple ducts  With the development of Levator palpabrae superioris, gland divides into orbital part  palpebral part  No tear production until third month after birth
  • 71. LACRIMAL SAC AND NASOLACRIMAL DUCT • Develop as solid cord of ectodermal cells between the nasal process and maxillary process of the developing face • The cord later canalizes – nasolacrimal duct • Superior end dilates to form lacrimal sac • Further cellular proliferation forms lacrimal ducts which enters each eyelid
  • 72. APPLIED ANATOMY  At junction of advancing cords there is a membranous plate, and it is at this site that block of NLD usually occurs in congenital NLD block  Incomplete canalization watering from eyeinfection of the lacrimal duct and sac
  • 73. ORBIT  Orbital bones  mesenchyme that encircles the optic vesicle  Medial wall – lateral nasal process  Lateral and inferior wall- maxillary process  Superior wall- mesenchymal capsule of forebrain  Posteriorly – from bones of base of skull  Orbital bones form in membrane, except those forming the posterior part which form in cartilage
  • 74. • Axis of orbitAt 1st month- 180 degrees laterally  At 2nd month - this angle begins to lessen  At 3rd month 72 degrees  Later stabilises at 45 degrees • Development of eyeball is at faster rate than of orbit; at 6th intrauterine life anterior half of eyeball projects beyond orbital opening
  • 75. Primordial tissues and its derivatives • Neuroectoderm • Surface ectoderm • Mesoderm
  • 76. SUMMARY OF OCULAR EMBRYOGENESIS rd week • Optic groove appears th week • Optic pit develops into opticvesicle • Lens plate forms • Embryonic Fissure develops st month • Lens pit then Lens vesicle form • Hyaloid vessels develop
  • 77. ½ month • Closure of embryonic fissure • Proliferation of neural retinal cells • Appearance of eyelid folds and nasolacrimal duct th week • Formation of embryonic nucleus of the lens • Sclera begins to form • Migration of waves of neural crest • First wave: formation of corneal and trabecular endothelium • Second wave: formation of corneal stroma • Third wave: formation of Iris stroma
  • 78. rd month • Differentiation of precursors of Rods and Cones • Anterior Chamber appears • Fetal nucleus starts to develop • Sclera condenses • Eyelid folds lengthen and fuse th month • Formation of Retinal vasculature begins • Hyaloid vessels begin to regress • Formation of physiological optic dsc and Lamina Cribosa • Canal of Schlemn appears • Bowman’s membrane develop • Formation of major arterial circle and spinchter muscle of Iris
  • 79. th month • Photoreceptors differentiate • Eyelid separation begins th month • Differentiation of dilator pupillae muscle • Nasolacrimal system becomes patent • Cones differentiate th month • Rods differentiate • Myelination of optic nerve begins • Posterior movement of anterior chamber angle • Retinal vessles start reaching nasal periphery
  • 80. th month • Completion of anterior chamber angle formation • hyaloid vessels disappear th month • Retinal vessels reach temporal periphery • Pupillary membrane disappears After birth • Macular region of the retina develops further
  • 81. REFERENCES  Peyman, Gholam A., Sanders and Goldberg, Principles and practice of Opthalmology(Vol.1),1st Edition,Jaypee:Delhi7,1987  Snell, Richard s. and Michael A. lemp, Clinical anatomy of the eye,2nd Edition, India:Blackwell science,1998.  Ramanjit Sihota, Radhika Tandon, Parson’s diseases of Eye- st Edition, Elsevier 2011  T.W. Sadler, Langman’s Medical Embryology, 9th Edition  Internet Resources