PURPOSE.To characterize the time course of normal foveal development in vivo in term infants and young children using handheld spectral-domain optical coherence tomography (HH-SDOCT). METHODS.We obtained 534 HH-SDOCT scans from 261 infants, children, and young adults with a mean age of 4.9 years (range, 0-27 years). Each retinal layer was manually segmented in ImageJ and correlated with gestational age (GA) and visual acuity (VA). The developmental trajectories of each retinal layer at the fovea, parafovea, and perifovea were calculated using fractional polynomial modeling.RESULTS. The central macular thickness (CMT) increases logarithmically between birth and 48.6 months GA. The foveal ganglion cell (GCL), inner plexiform, inner nuclear (INL), and outer plexiform layers decrease in thickness exponentially until 18 months GA. Interestingly, the parafoveal and perifoveal GCL and INL thicknesses initially decrease until 17 months GA and then increase in thickness until 65.5 GA. The foveal outer nuclear layer, inner segment, and outer segment of the photoreceptors increase in thickness logarithmically until 32.4, 26.9, and 45.3 months GA, respectively. The parafoveal and perifoveal outer retinal layers increase in thickness more gradually until 146 months GA. The thickness of the outer retinal layers and CMT were strongly correlated with VA, with r ¼ 0.54 (P < 0.0001) and r ¼ 0.52 (P < 0.0001), respectively. CONCLUSIONS.We have modeled for the first time the complex, nonlinear developmental trajectories for each retinal layer and demonstrate that development continues until adolescence. Our description of normal development will be helpful in diagnosing, monitoring, and understanding pediatric retinal disease.

Duane retraction syndrome (DRS) is a congenital eye-movement disorder defined by limited outward gaze and retraction of the eye on attempted inward gaze. Here, we report on three heterozygous loss-of-function MAFB mutations causing DRS and a dominant-negative MAFB mutation causing DRS and deafness. Using genotype-phenotype correlations in humans and Mafb-knockout mice, we propose a threshold model for variable loss of MAFB function. Postmortem studies of DRS have reported abducens nerve hypoplasia and aberrant innervation of the lateral rectus muscle by the oculomotor nerve. Our studies in mice now confirm this human DRS pathology. Moreover, we demonstrate that selectively disrupting abducens nerve development is sufficient to cause secondary innervation of the lateral rectus muscle by aberrant oculomotor nerve branches, which form at developmental decision regions close to target extraocular muscles. Thus, we present evidence that the primary cause of DRS is failure of the abducens nerve to fully innervate the lateral rectus muscle in early development.