Figure 4-6 and Table 4-2 outline the timeline of ocular development. Video 4-1 presents an animation of ocular embryology.
Animation developed by Evan Silverstein, MD.
Access all Section 2 videos at www.aao.org/bcscvideo_section02.
At 22 days, the optic primordium appears in neural folds. Two optic pits, derived from neuroectoderm, develop on either side of the midline and eventually form the optic vesicles. The narrow neck of these vesicles directly connects the optic vesicle and the developing forebrain. Once the optic vesicle touches the inner aspect of the surface ectoderm, the vesicle invaginates to form a bilayered optic cup. (Note that the embryologic optic cup is not the same as the anatomical optic cup of the optic nerve head.) The inner layer forms the neural retina, and the outer layer forms the retinal pigment epithelium (RPE) (see Fig 4-6D).
Table 4-1 Derivatives of Embryonic Tissues
As the optic cup forms, 2 processes take place. First, the surface ectoderm begins to invaginate to form the lens. Second, the area between the cup and the surface ectoderm fills with a combination of mesodermal and neural crest–derived cells—the ectomesenchyme that will form much of the anterior segment of the eye (see Fig 4-6E). In the area surrounding the posterior aspect of the optic cup, the same group of cells will give rise to the hyaloid vessels, choroid, and sclera (see Fig 4-6C–E).
Figure 4-6 Embryonic development of the eye. The contributions of the surface ectoderm, neuroectoderm, neural crest cells, and mesoderm are shown. RPE = retinal pigment epithelium.
(Illustration by Paul Schiffmacher. Adapted from Forrester JV, Dick AD, McMenamin PG, Roberts F, Pearlman E. The Eye: Basic Sciences in Practice. 4th ed. Edinburgh: Elsevier; 2016:104–105.)
Table 4-2 Chronology of Embryonic and Fetal Development of the Eye
Figure 4-7 Ocular and somatic development. A, Flexion of the neural tube and ballooning of the optic vesicle. B, Upper-limb buds appear as the optic cup and embryonic fissure emerge. C, Completion of the optic cup with closure of the fissure. Convolutions appear in the brain, and leg buds appear. Measurements show the size of the embryo. Bottom: Optic vesicle; optic cup with open embryonic fissure; cup with fissure closing.
The invagination of the optic cup occurs asymmetrically (Fig 4-7), with a ventral fissure that facilitates entry of mesodermal and neural crest cells. The fissure closes at its center first and then “zips” both anteriorly and posteriorly. Failure of fissure closure leads to a coloboma. Anterior colobomas are the most common (they cause iris and occasionally anterior scleral defects); central colobomas are the least common; and posterior colobomas occur with a frequency somewhere in between (they give rise to optic nerve head, retinal, and choroidal defects). The location of fissure closure correlates with the inferonasal quadrant, which is where colobomas are clinically found. See BCSC Section 6, Pediatric Ophthalmology and Strabismus, for further discussion of congenital and developmental disorders.
The following sections discuss development of individual ocular structures.
Lens formation begins with proliferation of surface ectoderm cells to form a lens plate, followed by inward invagination of the plate to form a lens pit. As the pit deepens, it closes anteriorly and detaches to form the lens vesicle (see Fig 4-6C). The remaining cells at the surface form the corneal epithelium (see Fig 4-6D). Invading neural crest cells form the corneal stroma and endothelium, along with other anterior segment structures (see Fig 4-6E).
The lens vesicle is a single-layer structure composed of cuboidal cells surrounding a large lumen, and it sits within the optic cup. The anterior cells remain cuboidal and single layered throughout life, but the rest of the lens epithelium cells become elongated, and their proliferation fills the optic vesicle. These cells form the primary lens fibers that eventually form the embryonal nucleus. The remaining outer cells create a true basement membrane known as the lens capsule (Fig 4-8).
Figure 4-8 Lens formation. A, Lens vesicle. B, Anterior cells remain cuboidal, whereas the posterior cells elongate. C, The posterior cells eventually fill the lens vesicle, giving rise to the embryonic nucleus. D, The anterior cells give rise to the lens epithelium (LE). Note the lens bow region (*) extending from the epithelial cells, giving rise to the secondary lens fibers (SLF). ALE = anterior lens epithelium; BM = basement membrane; PLF = primary lens fibers.
(Modified with permission from Forrester JV, Dick AD, McMenamin PG, Roberts F, Pearlman E. The Eye: Basic Sciences in Practice. 4th ed. Edinburgh: Elsevier; 2016:121–123.)
Development of the lens vesicle is supported by a branching network of vessels, derived from the hyaloid artery, known as the tunica vasculosa lentis. Failure of this tissue to regress can lead to conditions ranging from pupillary membranes that are seen on routine slit-lamp examination, to a malformation called persistent fetal vasculature (also called persistent hyperplastic primary vitreous), which can be associated with lenticular opacity and abnormal development of the eye. See also BCSC Section 6, Pediatric Ophthalmology and Strabismus.
The lens is a unique structure in that its basement membrane surrounds its cellular component. The lens capsule is transparent, thickest at its equator, and thinnest posteriorly. It is composed of type IV collagen and glycosaminoglycans (also known as GAGs). The elasticity of the lens capsule is key to facilitating changes in lens shape to achieve accommodation. The anterior lens (cuboidal) epithelium continues to form new lens fibers throughout life (see Fig 4-8D), leading to the lenticular thickening observed with age. The zonular fibers of the lens form as part of the tertiary vitreous, with mostly mesodermal and ectodermal contributions.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.