Ocular Embryology PDF

OCULAR EMBRYOLOGY Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD MAXON VISION CLINIC Objective: Provide a basic understanding of the structure and development of the eye Review the clinical assessment and management of ocular developmental abnormalities u le or. F malformat...

OCULAR EMBRYOLOGY Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD MAXON VISION CLINIC Objective: Provide a basic understanding of the structure and development of the eye Review the clinical assessment and management of ocular developmental abnormalities u le or. F malformations i l T ig a A Evaluate research evidence b outlining post-natal an e B i development, including visual acuity, ocular alignment, binocular eye movements, stereopsis, and refractive errors. Recognize ophthalmic signs related to premature birth Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD 3 Primary Germ Layers Ectoderm - single cell layer thick and proliferates forming a new outer transient layer of simple squamous le u F cells and epithelium called periderm T. i l a layer called the underlying proliferating b i g basal layer; outside e A layer i an B Mesoderm - gives rise to a loosely woven tissue called the mesenchyme; in between layer Endoderm - inside layer Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD 8th cell stage-Gastrulation(15th day) Ectoderm - NS tissue, skin, glands (epithelium)- esurface u l and neural. F i l T i g a b Mesoderm -nemuscles and A i a connectiveB tissue, BV; bones Endoderm - gut structures and some glandular tissue Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD NEURAL TUBE-neural ectoderm ANTERIOR- brain Forebrain– anterior telecephalon u le (cerebral hemispheres). F and i l T posterior diencephalon i g a (thalamus A b an e and eyes), B i C1 C2 Mid section– midbrain C3 C4 Hind-section – cerebellum, medulla oblongata and brainstem Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  INTRODUCTION week 3 - 10 - major development of the eye involves ectoderm, neural crest cells and le mesenchyme F u T. i l ig a A b neural tube e aectoderm n gives rise B i to the retina, iris, ciliary body epithelia, optic nerve, smooth muscle of the iris, and part of the vitreous humor Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  INTRODUCTION surface ectoderm gives rise to the lens, conjunctival and corneal epithelia, eyelids u le and. F lacrimal apparatus i l T ig a A b an e B i mesenchyme forms the other remaining structure Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  Eyes and Adnexa Early formation of the eye commences within the first month of gestation. Day 22 - 2 small groves develop l e on each F u side of the developing forebrain T. in the a i l neural folds (optic groove b i g / sulci) e A an On day 23, the ioptic pits appear on the B neural tube, which then develop into optic vesicles on day 25. Bulging of the diencephalon-future eye (failure lead to anophthalmos) Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  Eyes and Adnexa As the neural tube closes, these grooves become outpocketings and are now called optic vesicles. The optic vesicles extend from the forebrain e toward the l u mesenchyme.. surface ectoderm through the adjacentF i l T b i ga A i ne toward the surface ectoderm, As the optic vesicles grow a Bthe forebrain become attenuated, their connections to the proximal portion of the vesicle constricts to form optic stalks, which will eventually become the optic nerves and the distal portion invaginates to form the optic cup (future retina, iris, and ciliary body) Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Eyes and Adnexa The neural tube forms enclosed in it is the surface ectoderm ule. F Neural crest cellsg a are formedil T b i e A from the dorsal i an part of the tube B Bulging of the diencephalon outwards appears Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  Eyes and Adnexa Invagination of the optic vesicle begins and the neural ectoderm of the tube becomes bilayered u le F. il T iga The outer layer becomes the RPE b e A ianbecomes the neural retina The inner layer B Mesenchyme spread to fill the space between the ectoderm and neural ectoderm Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  Eyes and Adnexa The portion of each optic vesicle that interacts with the surface ectoderm induces that area of the ectoderm to form a thickening called the lens placode (a precursor of the lens). u le. F i T lbecome a lens pit, which The lens placode invaginates to i g a soon forms a complete circle A b that pinches off from the a n e i surface ectoderm to become B the lens vesicle. At the same time the lens vesicle is forming, the optic vesicle also invaginates to form a double-layered structure called the optic cup. So at this point we see a goblet-shaped optic cup with the lens vesicle oating in its open end Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD fl  Eyes and Adnexa The developing optic vesicle and stalk have a groove on their inferior surfaces called the optic or choroidal ssure, through which blood vessels gain access to the optic cup as well as the lens vesicle. ule. F a il T b ig The blood vessels are the hyaloid artery, a branch of the e A ophthalmic artery, and i an its accompanying vein. The B eventually fuse, completing the eye choroidal ssure will wall inferiorly and enclosing the vessels in a canal in the optic stalk. When the lens matures later on in fetal life, the distal end of the hyaloid artery will disintegrate and its proximal end will persist as the central retinal artery. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD fi fi  Retina (Gross structure) Invagination of the optic vesicle gives rise to the optic cup Outer layer-becomes pigmented l e and F u form the RPE i l T. i g a Inner layer-becomes A b the neural retina an e i Outer and inner B layer folds inward and come into contact but does not fuse Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  Retina (Gross structure) The two layers are unequal in size - the outer one is thinner than the inner one. The optic cup can be divided into two portions, the anterior 1/5 (rim) and the posterior 4/5. The rim area will ult mately form the iris and ciliary body, and the posterior 4/5 will form the retina u le The outer layer of the posterior 4/5 will become the pigment layer of the retina, and the inner one will. F become the neural retina. These two layers are separated by the intraretinal space il T i g a A b an e B i i­  Retina (Gross structure) The development of the retinas pigment layer is very straightforward, with the appearance of melanin granules in the cells of this layer at around 4 1/2 weeks. 6 weeks - the cells in the posterior aspect of the inner layer of the optic cup begin a more complicated process. The cells immediately adjacent to the intraretinal space begin to differentiate into the photoreceptors (rods and cones). The next layer of cells will become the Muller supporting cells and the bipolar neurons, and the innermost super cial layer will develop into the axons of the ganglion cells This means light actually passes through the neuronal layers before reaching the rods and cones. The ganglion cell bers gradually ll in the lumen of the optic stalk as it becomes the optic nerve. 8 months - all the layers of the retina that you will see in your Histology course are recognizable. But maturation of the photoreceptors continues after birth, which in part explains why a baby’s visual acuity improves as he or she grows. fi fi fi  Retina (Gross structure) Outer neuroblastic layer forms - Horizontal cells, rods and cones u le F Inner neuroblastic layerT.forms - ganglion, a i l amacrine and Muller big bers e A i an B Layer of the retina the macula rst develops - ganglion cells Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD fi fi  Retina (Gross structure) Microphthalmos- N. ectoderm fail to fuse with surface ectoderm u le Congenital cystic eye-OV T. F a i l i g invagination failure e A b i a n CongenitalBRetinal non- attachment –inc OV invagination Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Crystalline Lens Component of the surface ectoderm that invaginates the optic cup forms a ball of epithelial cells that become u l e the lens. F Lens epithelial cellsasecrete i lT a b i g membrane that e A becomes the capsule i a n B Posterior epithelial cells extend towards the front to occupy the space within the ball of cells (primary lens fibers) Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Crystalline Lens At about the same time as the pigmented layer of the retina is developing, the cells of the posterior part of the lens vesicle transform into u le elongated, slender primary. lens F fibers. i l T i g a A b These new cells fill n e a in the previously hollow B i structure. About four weeks later, more lens fibers develop, this time from the anterior wall of the lens vesicle (secondary lens fibers). Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Crystalline Lens The fist set of equatorial epithelial cells elongate to surround the primary fibers (secondary lens fibers) u le. F i l T More secondary fibers i g a are laid down A b and compress e anthe early cells toward the B i center (tertiary lens fibers) The points at which the cell meet at the front and back are called Y sutures Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  Lens APHAKIA – failure of SE to invaginate CATARACT – failure of the PLF to u le elongate and abnormal F. disposition of i l T a the lens fibers Abig n e PETER’s ANOMALY B ia – failure of the lens stalk to disintegrate and release the ball of epithelial cells Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  RETINA (FINE STRUCTURES) The outer layer of the optic cup remains as a single layer and becomes the pigment epithelium of the retina. u le The inner layer of the optic cup undergoes a complicated F. of the retina. This occurs differentiation into the other nine layers i l T a igthe seventh month, the outermost slowly throughout gestation. By A b cell layer (consisting of the a n e nuclei of the rods and cones) is present as well as the bipolar,B i amacrine, and ganglion cells and nerve fibers. The macular region is thicker than the rest of the retina until the eighth month, when macular depression begins to develop. Macular development is not complete in anatomic terms until 6 months after birth. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD RETINA (FINE STRUCTURES) The cells of the optic stalk become the optic nerve ule The outer cup lay down pigment F T. i The inner cup divide repeatedly a l to form a dense b ig A closest to the RPE, with cellular area (6-7 ecells) i a n B adjacent to the basement an acellular zone membrane (ILM) Cells migrate through the empty zone towards the basement membrane to form the inner and outer neuroblastic layers Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD RETINA (FINE STRUCTURES) Cells migrate from both the blastic layers toward the center to form the inner nuclear layer Empty areas either side fill with cell processes and become the plexiform layers (IPLuland e OPL) and the. F the GERM CELL INB produces ganglion cells to i l T form i g a layer b A Cells in the outeria n e nuclear layer put a cilium from which the outerBsegments develop to form the photoreceptors The ganglion cells put out their axon which run across the retina surface to form the nerve fiber layer (28 weeks) Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  Optic Nerve and Retinal Vessels The axons of the ganglion cells of the retina form the nerve fibre layer. The fibres slowly form the optic stalk at 7 weeks, and then the optic nerve. Myelination extends from the brain peripherally down the optic nerve, and at birth has reached the lamina cribrosa. u le. F T Long ciliary arteries bud off from the hyaloid system at 6 weeks il and interconnect around the optic i g acup margin with the major circle A b of the iris by 7 weeks. Thee hyaloid artery gives rise to the central i a n retinal artery and itsBbranches at 4 months. Buds of blood vessels arise in the region of the optic disc and gradually extend to the peripheral retina, reaching the ora serrata at 8 months. The hyaloid system has atrophied completely by the eighth month. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  ANTERIOR STRUCTURES Mesenchyme between the rim of the cup and surface ectoderm migrates between lens and surface ectoderm Sedimentation of this mesenchyme on the e surface ectoderm u l (Corneal epithelium) forms the corneal. F endothelium (neural crest cells) and then stroma i l T i g a A b Adjacent cells are breaking a n e down to form the anterior chamber B i The rim of the cup extends forward between the mesenchyme and the anterior lens surface The anterior chamber is deepening and moving peripherally to from the angle Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  ANTERIOR STRUCTURES During the sixth and seventh weeks the mesenchyme that surrounds the external surface of the optic cup condenses into two u le layers, an inner,. F pigmented, vascular layer known i l T as the choroid i g a Ab called the sclera. and an outer, fibrous layer e ia n B The mesenchyme that is anterior to the developing lens splits into two layers that surround the newly formed anterior chamber of the eye Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD ANTERIOR STRUCTURES The inner layer is continuous with the choroid and is called the iridopupillary membrane and the outer layer is continuous with the sclera. u le The outer layer will form the substantia propria, or stroma of the cornea.. F i The anterior segment of the globe is formed T l by migration of neural crest a ig ectoderm, which develops into b cells into the space between the surface A vesicle, which has become separated the corneal epithelium, and the lens an e from it. B i The layers of the cornea, and the corneoscleral junction, are present by 4 months. The anterior chamber appears at 7 weeks, and is very shallow until birth. The anterior chamber angle, including the trabecular meshwork, develops from a condensation of mesenchyme at the anterior edge of the optic cup. The aqueous outflow system is ready to function prior to birth. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Iris and Ciliary Body the anterior rim of the optic cup gives rise to the non pigmented epithelium u le of the iris and the epithelium. F of the i l T ciliary body (inner b i g a layer of the posterior 4/5 of e A the optic cup forms i a n the neuralBretina of the eye) outer layer forms the pigmented layer Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Iris and Ciliary Body the stroma of the iris and ciliary body develop from neural crest cells that migrate into the area ule develop from the sphincter and dilator pupillae F the optic cup neuroectoderm T. a i l b i g A e derived from the the ciliary musclea nis mesenchyme Bi the color of the iris is determined by the amount of melanin distributed in the stroma of the iris (posterior epithelium) Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Iris and Ciliary Body Microcoria - failure of the dilator pupillae muscle to form ule. F g ail T b i Aniridia - failure n e A of the rim of the i a B optic cup to develop Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Choroid At the 6 mm (31/2 week) stage, a network of capillaries encircles the u le optic cup and develops. F into the choroid. i l T b i ga e A ia n By the third month, the intermediate B and large venous channels of the choroid are developed and drain into the vortex veins to exit from the eye. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD UVEA, VITREOUS and SCLERA the vitreous body forms in the center of the optic cup posterior to the lens u le. F vitreous is comprised of i T l a gel-like substance i g a called vitreous humor b A derived from n e acells mesenchymal B i of neural crest origin more vitreous humor is added by the neuroectoderm of the optic cup Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  UVEA, VITREOUS and SCLERA Secondary vitreous is secreted by the mesenchyme and compresses the primary vitreous and remains of the hyaloid vasculature into a thin column that runs from the retina to the back surface of the lens called CLOQUET’S canal u le. F Collagen secreted by mesenchyme that surrounds the neuro- i l T ectodermal cup forms the sclera. ig a A b e an muscles take shape from i The sclera and extraocular B surrounding the optic cup and become condensed mesenchyme recognizable by the 7th week. By the fourth month, the development of these structures is well underway. Tenon's capsule becomes apparent around the insertions of the rectus muscles at 12 weeks and reaches completion by 5 months. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD UVEA, VITREOUS and SCLERA Group of mesoderm cells invade the sclera to form the EOM u le. F il T iga sclera and RPE, the Between the developing b mesenchyme and e A the external vasculature i n a the choroid B combine to form Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD ADNEXA 6th week - eyelids begin to form from the neural crest cells as well as surface ectoderm just anterior to the cornea u le. F il T Ectoderm peripheraligato the cornea in now A b induced to formne2 simple folds (EYELIDS) i a B As they extend, they come together and fuse 27th week - eyelids separate (palpebral fissure) Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD ADNEXA The meibomian gland and accessory glands of the lids form from u lelid epithelial cells that migrate into the. Flid stroma i l T i g a A b The lacrimal glanda n e is formed by an B i epithelial invasion of the prospective orbital space by epithelial cells at the apex of the fold (tarsal conjunctiva) Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  Extraocular Muscles develop from three preotic somites. These are the somites founds anterior to the developing ear of the embryo. u le. F Each preotic somite is supplied i l T by its own g a bi VI) supply the cranial nerve. (III, IV,Aand a n e i extraocular muscles. B So the somite which is supplied by the III cranial nerve forms 4 of the 6 extraocular muscles while the remaining two each give rise to one muscle each. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  AGE OF THE SIZE OF THE OCULAR STRUCTURE EMBRYO (WKS) EMBRYO (mm) 3 2.5 BULGE IN DIENCEPHALON WALL 4 3.5 u leOPTIC VESICLE. F 4.5 7 il T OPTIC CUP i g a 5 8 Ab LENS VESCIVLE,RPE, CORNEAL an e EPITHELIUM, PRIMARY B i VITREOUS 5.5 10 HYALOID ARTERY, AND NERVE FIBERIN FISSURES 6 13 COMMENCEMENT OF NEURAL RETINAL DIFFERENTIATION 6.5 15 LENS VESICLE CAVITY FILLED WITH PRIMARY FIBRE CELLS 6.75 18 CORNEAL ENDOTHELIUM  AGE OF THE SIZE OF THE OCULAR STRUCTURE EMBRYO (WKS) EMBRYO (mm) 6.75 18 CORNEAL ENDOTHELIUM 7.5 20 GAGLION AXONS REACH LGN, CONRAL STROMA 7.75 25 SCLERAL SEDIMENTS 8.5 30 SECONDARY VITREOUS u l e 12 50. F HYALOID VASCULATURE il T DISINTEGRATE i g a 16 90 Ab IRIS AND CILIARY PROCESS an e FORM, SPHINCTER EVIDENT 24 B i 200 RETINA COMPONENTS COMPLETE, CHORIOD FORMED, IRIS DILATOR PRESENT 32 280 TRABECULAR MESH AND ANGLE COMPLETE 36 400 RETINAL VASCULATURE COMPLETE, IRIS FULLY PIGMENTED, PUPILLARY MEMBRANE DISINEFRATES DERIVATIVES OF VARIOUS LAYERS NEUROECTODERM Pigmented epithelia of retina ( 1 layer), ciliary body (1 Flayer), ule and iris (2 layers). T. a i l b ig Sensory retina, e Aand innermost i a n (nonpigmented) B layer of ciliary body Optic nerve Iris sphincter and dilator muscles Vitreous (part) Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD DERIVATIVES OF VARIOUS LAYERS SURFACE ECTODERM Lens Corneal epithelium Fule T. Conjunctiva and a i l caruncle b ig Eyelid skin e A i an B Lacrimal apparatus (glands and drainage system) Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  DERIVATIVES OF VARIOUS LAYERS Head mesenchyme (neural crest and/or mesoderm) Blood vessels-m Corneal stroma-m, descemets and u le endothelium-n Stroma of choroid-m ciliaryTbody-n.F and iris-n a i l Ciliary muscle-m b i g e A Sclera-m i a n B (meninges)-n Optic nerve sheath Extraocular muscles and fasciae-m Remainder of the eyelids (orbicularis oculi muscle, tarsus, orbital septum, etc)-m Vitreous (part)-n Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Congenital abnormalities of the eye 1. Coloboma This is a condition in which the choroid fissure does not completely close as it should in u lethe seventh week and therefore there is a defectT.inFthe inferior part of a the iris which gives a keyhole i l appearance to the pupil. ig b e A i a n Sometimes the defect B can include the retina as well which can compromise vision. Coloboma can be caused by environmental factors or it can be transmitted as an autosomal dominant gene. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Congenital abnormalities of the eye 2. Congenital Glaucoma Since glaucoma is a result of the abnormally high intraocular pressure, congenital u le glaucoma can be causedl Tby. F abnormal g a i b i development of the iridocorneal angle e structures thatiaareA n responsible for the B of fluid. proper drainage This can be caused by a rubella infection or by recessive mutant genes. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Congenital abnormalities of the eye 3. Congenital Cataracts le lens fibers. Again This is due to improper growth of the u. it can be caused by a rubella infectionF in the mother, T ail infection occurs after depending on the timing - ifigthe the lens has developed then A b the cataracts do not form. a n e B i It is important for this anomaly to be corrected within the first year of life otherwise the further development of the retina will not take place because proper connections between the optic nerve and the brain cannot be established. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Congenital abnormalities of the eye 4. Congenital Detached Retina le This occurs when the intraretinal space persists. u Recall that this is the space between. F the pigment i l T i g a epithelium and the light sensitive portion of the retina. A b e an B i Although the pigment layer is strongly attached to the underlying choroid layer, there is never a strong attachment between the two layers of the retina which is why a severe blow to the head can also cause a non- congenital detached retina. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Congenital abnormalities of the eye 5. Partially Persistent Iridopupillary membrane u le This occurs when the T.F iridopupillary a i l membrane that covers b ig the lens for a e A brief period in i n autero does not dissolve. B If so, web-like strands of tissue can be seen over the pupil in newborns. It is asymptomatic. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD  u le. F il T i g a Ab an e B i Congenital abnormalities of the eye 6. Persistent Hyaloid artery the hyaloid artery initially supplies both the lens and the retina. ule F. g il T a vessel disappears and i Then the distal part of this b the proximal portion e A becomes the central artery of i a n the retina. B When the distal end does not disappear completely there is impairment of vision and possibly hemorrhages into the eye. (consistent floater) Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Congenital abnormalities of the eye 7. Microphthalmia the presence of an unusually small eye. It may be associated with other u l e ocular defects.. F i l T a ig face that is affected is Usually the side of the A b underdeveloped. an e B i A common cause of this condition is infection by rubella virus, HIV and herpes simplex virus. Some drugs can also cause it. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD Congenital abnormalities of the eye 8. Peter’s Anomaly is due to a persistent lens stalk. le thinning and clouding of the cornea due to dysgenesis of the u anterior segment during development. F i l T i g a This means that the lens vesicle A b does not pinch off from the a n e surface ectoderm and therefore a fairly normal looking eye develops except for aB i white mass where the undersurface of the cornea is connected to the ant rior aspect of the lens by a stalk. This occurs in about 1:10000 people. It has been linked to mutations in the gene encoding pax6, a homeobox transcription factor important for lens formation. Biane Abigail T. Fule, OD, FCIRC, CA-OEP, M-COVD e­ Peter’s anomaly