Figure 15-5 A, Layers of late-gestation fetal human retina. Development of the human fovea at (top left) Fwk 28, (top right) Fwk 34, (bottom left) Fwk 35, and (bottom right) Fwk 37. A transient layer of Chievitz (TC) is present as a gap in the INL of all eyes from this age group. The foveal pit (P) has thinned the GCL, IPL, and INL compared to layers surrounding the pit (the foveal slope). Scale in bottom left for all. GCL = ganglion cell layer; INL = inner nuclear layer; IPL = inner plexiform layer; NFL = nerve fiber layer; ONL = outer nuclear layer; OPL = outer plexiform layer; RPE = retinal pigment epithelium. B, Layers and histology of human retina during childhood. The final maturation stages of the human fovea are shown at (top left) 3.8 years and (top right) 13 years with higher magnification of the 13 years (middle) foveal center, (bottom left) first rods at 300 μm, (bottom middle left) 500 μm, and (bottom middle right) 2 mm from the fovea. The foveal pit is wide and shallow. The foveal center is composed of long, thin cone OS; IS, and cell bodies 8–12 cones deep. The central OPL contains a thick layer of axon (Ax). The foveal OPL contains only Ax (OPL*) out to 500 μm, where synaptic pedicles (bottom middle left, OPL; bottom middle and far right, S) are first encountered. Long, thin rod OS (bottom row, black arrows) becomes more prominent with eccentricity. Note the marked increase in cone IS diameter from the foveal center to 300 μm, with a small further increase at 2 mm. Scale in middle for top and middle rows; scale in bottom left for bottom row. C = cone; ELM = external limiting membrane; GCL = ganglion cell layer; INL = inner nuclear layer; IPL = inner plexiform layer; IS = inner segment; OS = outer segment; NFL = nerve fiber layer; ONL = outer nuclear layer; OPL = outer plexiform layer; R = rod; RPE = retinal pigment

epithelium. (Modified with permission from Hendrickson A, Possin D, Lejla V, Toth CA. Histologic development of the human fovea from midgestation to maturity. Am J Ophthalmol. 2012;154(5):767–778.)

Visual Acuity and Stereoacuity

Two major methods are used to quantitate visual acuity in preverbal infants and toddlers: preferential looking (PL) and visually evoked potential (VEP). See Chapter 1 for a description of these methods. VEP shows that visual acuity improves from approximately 20/400 in newborns to 20/20 by age 6–7 months. However, PL studies estimate the visual acuity of a newborn to be 20/600, improving to 20/120 by age 3 months and to 20/60 by 6 months. Further, PL testing shows that visual acuity of 20/20 is not reached until age 3–5 years. The discrepancy between measurements obtained by these 2 methods may be related to the higher cortical processing required for PL compared to VEP. Stereoacuity reaches 60 seconds of arc by about age 5–6 months (see Chapter 7).

Abnormal Growth and Development

Major congenital anomalies occur in 2%–3% of live births. Causes include chromosomal anomalies, multifactorial disorders, environmental agents, and idiopathic etiologies. Regardless of etiology, from a developmental point of view, congenital anomalies may be categorized as follows (ocular examples are given in parentheses):

agenesis: developmental failure (anophthalmos) hypoplasia: developmental arrest (optic nerve hypoplasia) hyperplasia: developmental excess (distichiasis) dysraphia: failure to fuse (choroidal coloboma)

failure to divide or canalize (congenital nasolacrimal duct obstruction) persistence of vestigial structures (persistent fetal vasculature)

A malformation implies a morphologic defect present from the onset of development or from a very early stage. A disturbance to a group of cells in a single developmental field may cause multiple malformations. Multiple etiologies may result in similar field defects and patterns of malformation. A single structural defect or factor can lead to a cascade, or domino effect, of secondary anomalies called a sequence. The Pierre Robin group of anomalies (cleft palate, glossoptosis, micrognathia, respiratory problems) may represent a sequence caused by abnormal descent of the tongue and is seen in disorders such as Stickler and fetal alcohol syndromes. A syndrome is a recognizable and consistent pattern of multiple malformations known to have a specific cause, which is usually a

mutation of a single gene, a chromosome alteration, or an environmental agent. An association represents defects known to occur together in a statistically significant number of patients. An association may represent a variety of yet-unidentified causes. Two or more minor anomalies in combination significantly increase the chance of an associated major malformation.

Jones KL, Jones MC, del Campo M. Smith’s Recognizable Patterns of Human Malformation. 7th ed. Philadelphia: Elsevier Saunders; 2013.