Foveal Differentiation and Inner Retinal Displacement Are Arrested in Extremely Premature Infants.

Purpose: Children with a history of prematurity often have poorly developed foveae but when during development foveal differences arise. We hypothesize that the course of foveal development is altered from the time of preterm birth. Methods: Eyes of 102 preterm infants undergoing retinopathy of prematurity screening examinations in the STudy of Eye imaging in Premature infantS (BabySTEPS) (NCT02887157) were serially imaged between 30 and 42 weeks postmenstrual age (PMA) using handheld optical coherence tomography systems. Total retinal thickness, inner retinal layer (IRL) thickness, and outer retinal layer (ORL) thickness were measured at the foveal center and parafovea. Foveal put depth, IRL thickness, and ORL thickness were compared between infants born at different gestational ages using mixed effects models. Results: Foveal pit depth and IRL thickness were inversely related to gestational age; on average, the most premature infants had the thickest IRL and shallowest pits at all PMAs. Differences were evident by 30 weeks PMA and persisted through 42 weeks PMA. The foveal pits of the most premature infants did not progressively deepen, and the IRLs did not continue to thin with increasing chronological age. Conclusions: Foveation in extremely preterm infants is arrested from the earliest observed ages and fails to progress through term equivalent age. The developmental displacement of the IRL from the foveal center into the parafovea does not occur normally after preterm birth. These observations suggest that foveal hypoplasia seen in children with history of prematurity is due to disturbances in foveal development that manifest within weeks of birth.

The potential role of Arhgef33 RhoGEF in foveal development in the zebra finch retina.

The fovea is a pit formed in the center of the retina that enables high-acuity vision in certain vertebrate species. While formation of the fovea fascinates many researchers, the molecular mechanisms underlying foveal development are poorly understood. In the current study, we histologically investigated foveal development in zebra finch (Taeniopygia guttata) and found that foveal pit formation begins just before post-hatch day 14 (P14). We next performed RNA-seq analysis to compare gene expression profiles between the central (foveal and parafoveal) and peripheral retina in zebra finch at P14. We found that the Arhgef33 expression is enriched in the middle layer of the inner nuclear layer at the parafovea, suggesting that Arhgef33 is dominantly expressed in Müller glial cells in the developing parafovea. We then performed a pull-down assay using Rhotekin-RBD and observed GEF activity of Arhgef33 against RhoA. We found that overexpression of Arhgef33 in HEK293 cells induces cell contraction and that Arhgef33 expression inhibits neurite extension in Neuro 2A cells, which is partially recovered by a Rho-kinase (ROCK) inhibitor. Taken together, we used zebra finch as a model animal to investigate foveal development and identified Arhgef33 as a candidate protein possibly involved in foveal development through modulating RhoA activity.

Circuit Reorganization Shapes the Developing Human Foveal Midget Connectome toward Single-Cone Resolution.

The human visual pathway is specialized for the perception of fine spatial detail. The neural circuitry that determines visual acuity begins in the retinal fovea, where the resolution afforded by a dense array of cone photoreceptors is preserved in the retinal output by a remarkable non-divergent circuit: cone → midget bipolar interneuron → midget ganglion cell (the "private line"). How the private line develops is unknown; it could involve early specification of extremely precise synaptic connections or, by contrast, emerge slowly in concordance with the gradual maturation of foveal architecture and visual sensitivity. To distinguish between these hypotheses, we reconstructed the midget circuitry in the fetal human fovea by serial electron microscopy. We discovered that the midget private line is sculpted by synaptic remodeling beginning early in fetal life, with midget bipolar cells contacting a single cone by mid-gestation and bipolar cell-ganglion cell connectivity undergoing a more protracted period of refinement.

In vivo assessment of foveal geometry and cone photoreceptor density and spacing in children.

The fovea undergoes significant developmental changes from birth into adolescence. However, there is limited data examining cone photoreceptor density, foveal pit shape, and foveal avascular zone (FAZ) size in children. The purpose of this study was to determine whether overall foveal structure differs as a function of age and refractive status in children. Forty-eight healthy children (ages 5.8 to 15.8 years) underwent optical coherence tomography imaging to quantify foveal point thickness and foveal pit diameter, depth, and slope. Adaptive optics scanning laser ophthalmoscope (AOSLO) images of foveal capillaries and cone photoreceptors were acquired in a subset of children to quantify FAZ metrics and cone densities at 0.2, 0.3, and 0.5 mm eccentricities. Results show that foveal pit and FAZ metrics were not related to age, axial length, or refractive status. However, linear cone density was lower in myopic versus non-myopic children at eccentricities of 0.2 mm (mean ± SD = 50,022 ± 5,878 cones/mm2 vs 58,989 ± 4,822 cones/mm2, P < 0.001) and 0.3 mm (43,944 ± 5,547 cones/mm2 vs 48,622 ± 3,538 cones/mm2, P < 0.001). These results suggest FAZ and foveal pit metrics do not systematically differ with age in children, while myopic eyes have decreased linear cone density near the foveal center. Significance Statement: The development of the fovea begins prior to birth and continues through the early teenage years until it reaches adult-like properties. Although the majority of changes during childhood are related to the maturation and migration of cone photoreceptors, in vivo data describing cone packing in children is limited. We assessed overall foveal structure in children as young as 5.8 years old by quantifying cone density and spacing, foveal avascular zone size, and foveal pit morphometry to investigate potential structural differences as a function of age and refractive status. While foveal avascular zone and foveal pit metrics did not significantly differ with age, results indicate that myopic children have lower linear cone densities close to the foveal center compared to non-myopic children.

Effect of Prematurity on Foveal Development in Early School-Age Children.

PURPOSE: To evaluate the foveal development in preterm children with optical coherence tomography and OCT angiography. DESIGN: Retrospective cohort study. METHODS: This study included children aged 6-8 years who were born prematurely and who did not receive retinopathy treatment. They were evaluated between September 2018 and July 2019, categorized according to gestational age (GA) (group I: GA ≤30 weeks; group II: GA between 31 and 34 weeks), and compared with full-term children (group III). Central foveal thickness (CFT), inner retinal thickness (IRT), outer retinal thickness (ORT), subfoveal choroidal thickness (CT), temporal and nasal CT, foveal avascular zone (FAZ) diameter, and vessel densities of superficial (SCP-VD) and deep capillary plexuses (DCP-VD) of the foveal and parafoveal areas were examined in detail. RESULTS: The study included 126 eyes of 63 patients (group I: 40 eyes; group II: 46 eyes; and group III: 40 eyes). In group I, CFT, IRT, ORT, foveal SCP-VD, and foveal DCP-VD were significantly greater than those in the other groups, and temporal CT and FAZ diameter were significantly lower (P < .05). GA showed a significant negative correlation with CFT, IRT, ORT, foveal SCP-VD, and foveal DCP-VD and a significant positive correlation with subfoveal CT, temporal and nasal CT, and FAZ diameter (P < .05). CONCLUSION: The morphological and vascular foveal structures in early school-age children who were born premature were different from those of full-term children. These differences were correlated with GA and more pronounced in those with GA of ≤30 weeks.

Phenotypic Spectrum of the Foveal Configuration and Foveal Avascular Zone in Patients With Alport Syndrome.

Purpose: To investigate characteristics of the foveal pit and the foveal avascular zone (FAZ) in patients with Alport syndrome (AS), a rare monogenetic disease due to mutations in genes encoding for collagen type IV. Methods: Twenty-eight eyes of nine patients with AS, and five autosomal-recessive carriers and 15 eyes from 15 age-similar healthy control subjects were examined using optical coherence tomography (OCT) and OCT-angiography (OCT-A). Foveal configuration and FAZ measures including the FAZ area, circularity, and vessel density in the central 1° and 3° were correlated. Results: Foveal hypoplasia was found in 10 eyes from seven patients with either genotype. In contrast, a staircase foveopathy was found in seven eyes of four X-linked AS patients. The average FAZ area did not differ significantly between AS patients and control subjects (mean ± SD 0.24 ± 0.24 mm2 vs. 0.21 ± 0.09 mm2; P = 0.64). Five eyes showed absence or severe anomalies of the FAZ with crossing macular capillaries that was linked to the degree of foveal hypoplasia on OCT images leading to a significant inverse correlation of FAZ area and foveal thickness (r = -0.88; P < 0.001). In contrary, female patients with X-linked mutations exhibited a significantly greater FAZ area (0.48 ± 0.30 mm2 vs. 0.21 ± 0.09 mm2; P = 0.007), in line with OCT findings of a staircase foveopathy. Conclusions: The foveal phenotypic spectrum in AS ranges from foveal hypoplasia and absence of a FAZ to staircase foveopathy with an enlarged FAZ. Because the development of the FAZ and foveal pit are closely related, these findings suggest an important role for collagen type IV in foveal development and maturation.

Optical Coherence Tomography Findings After Childhood Lensectomy.

Purpose: To explore the impact of childhood lensectomy on posterior segment development. Methods: Cross-sectional observational study at children's eye clinics at a tertiary referral center in London, UK. We included 45 children age 4 to 16 years with healthy eyes and 38 who had undergone lensectomy. We acquired posterior segment optical coherence tomography scans of both eyes. We used parametric and nonparametric tests in SPSS24 for the comparison of parameters between groups and within individuals; a P value less than 0.05 was considered significant. The main outcome measures were foveal pit depth and subfoveal choroidal thickness (CT). Secondary outcomes were inner and outer ring CT and photoreceptor layer parameters, macular and peripapillary retinal nerve fiber layer thickness. Results: Foveal pit depth and subfoveal CT are significantly reduced in eyes that have undergone lensectomy compared with nonoperated eyes. Inner ring CT and outer ring CT are reduced. Foveal inner retinal layer thickness is increased. Mean inner retinal and outer nuclear layer thickness are not affected. Conclusions: Childhood lensectomy is associated with a reduction in developmental foveal pit deepening and lack of developmental thickening of the posterior choroid. Mechanical and optical disruption of foveal and subfoveal choroidal development may affect structural foveal development after childhood lensectomy.

Foveal Development After Use of Bevacizumab for Aggressive Posterior Retinopathy of Prematurity.

Foveal development can occur after intravitreal bevacizumab (IVB) treatment for aggressive posterior retinopathy of prematurity (APROP). A 1,310 g male twin, born at 31 weeks, was diagnosed with APROP and undeveloped fovea at 33 weeks. IVB was injected in both eyes. Unfortunately, multiple surgical interventions were required to treat retinal detachment in the left eye, at which time, foveal development was studied in the right eye. Imaging revealed development of foveal capillary ring, avascular zone, and shallow pit. Although bevacizumab is an inhibitor of angiogenesis and delays vascular advancement, development of foveal capillary vascular network with foveal avascular zone and pit can proceed despite multiple treatments. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e185-e187.].

Anolis carolinensis as a model to understand the molecular and cellular basis of foveal development.

The fovea is an anatomical specialization of the central retina containing closely packed cone-photoreceptors providing an area of high acuity vision in humans and primates. Despite its key role in the clarity of vision, little is known about the molecular and cellular basis of foveal development, due to the absence of a foveal structure in commonly used laboratory animal models. Of the amniotes the retina in birds of prey and some reptiles do exhibit a typical foveal structure, but they have not been studied in the context of foveal development due to lack of availability of embryonic tissue, lack of captive breeding programs, and limited genomic information. However, the genome for the diurnal bifoveate reptile species Anolis carolinensis (green anole) was recently published and it is possible to collect embryos from this species in captivity. Here, we tested the feasibility of using the anole as a model to study foveal development. Eyes were collected at various stages of development for histological analysis, immunofluorescence, and apoptosis. We show that at embryonic stage (ES) 10 there is peak ganglion cell density at the incipient central foveal region and a single row of cone photoreceptor nuclei. At ES17 the foveal pit begins to form and at this stage there are 3-4 rows of cone nuclei. Post-hatching a further increase in cone density and lengthening of inner and outer segments is observed. A yellowish pigment was seen in the adult central foveal region, but not in the temporal fovea. At ES14 Pax6 was localized across the entire retina, but was more prominent in the ganglion cell layer (GCL) and the part of the inner nuclear layer (INL) containing amacrine cell bodies. However, at ES17 Pax6 expression in the ganglion cells of the central retina was markedly reduced. Bioinformatic analysis revealed that 86% of human candidate foveal hypoplasia genes had an orthologous gene or DNA sequence in the green anole. These findings provide the first insight into foveal morphogenesis in the green anole and suggest that it could be a very useful model for investigating the molecular signals driving foveal development, and thus inform on human foveal development and disease.

[The Impact of Macular Development on Full-field and Multifocal ERG in Extremely Preterm-born Children with and without Acute Retinopathy of Prematurity]. / Einfluss der Makulareifung auf Ganzfeld- und multifokales ERG bei ehemaligen Extremfrühgeborenen mit und ohne akute Frühgeborenenretinopathie.

Introduction Retinal development is a complex process that can continue into early childhood and beyond. Prematurity can affect the maturation of the central retina, characterised by a flatter foveal pit and overlying inner retinal layers (IRL), leading to a disturbed ratio of outer retinal layers to IRL ("macular developmental arrest": MDA) and functional impairment (Bowl et al. 2016 18). The purpose of this study was to correlate functional results by electrophysiology with the morphological appearance of the fovea in children with spontaneously regressed and without ROP and term-born age-matched controls. Methods We investigated n = 60 preterm-born children with spontaneously regressed (srROP, n = 15) and without ROP (noROP, n = 50) as part of an extensive prospective cohort study and compared them to n = 10 term-born age-matched controls (Term). Full-field electroretinogram (ffERG) and multifocal ERG (mfERG) based on ISCEV-standards were performed in every child for functional evaluation. Foveal morphology was evaluated with optical coherence tomography (SD-OCT, Spectralis, Heidelberg Engineering, Germany). Results Analysis of the scotopic ffERG showed significantly modified b-wave amplitudes in srROP and noROP, especially when MDA was found on SD-OCT. The mfERG exhibited a modified P1-component of the central hexagon and the second concentric ring in children with MDA. No other parameters were significantly changed. Conclusions Electrophysiological changes can be found in extremely preterm-born children, especially with OCT-confirmed foveal maturation impairment (MDA), namely in children with spontaneously regressed ROP as well as in children without ROP. The reduced b-wave in the scotopic ffERG and the reduced P1-component in the mfERG indicate involvement of bipolar cells in extremely prematurely born children with MDA. In particular, the correlation of MDA with ffERG could be a sign of more global retinal maturation disturbance accompanying MDA, and this is seen even without acute ROP.

Postnatal maturation of the fovea in Macaca mulatta using optical coherence tomography.

Changes in the foveal anatomy during infancy are an important component in early development of spatial vision. The present longitudinal study in rhesus monkeys was undertaken to characterize the postnatal maturation of the fovea. Starting at four weeks after birth, the retinas of the left eyes of sixteen infant monkeys were imaged using spectral domain optical coherence tomography (SD OCT). Retinal scans were repeated every 30 days during the first year of life and every 60 days thereafter. Volume scans through the fovea were registered, scaled using a three surface schematic eye, and analyzed to measure foveal pit parameters. The individual layers of the retina were manually segmented and thicknesses were measured over a transverse distance of 1250 microns from the center of the foveal pit. Based on infrared scanning laser ophthalmoscope (IR SLO) images acquired with the SD OCT system, there were significant changes in the extent of the retina scanned as the eyes matured. Using a three-surface schematic eye, the length of each scan could be computed and was validated using image registration (R2 = 0.88, slope = 1.003, p < 0.05). Over the first 18 months of life, the mean retinal thickness at the pit center had increased by 21.4% with a corresponding 20.3% decrease in pit depth. The major changes occurred within the first 120 days, but did not stabilize until a year after birth. In Macaca mulatta infants, the primary anatomical maturation of the fovea occurs within the first few months of life, as determined by longitudinal data from SD OCT measurements. The timelines for maturation of the fovea correspond well with the normal development of the lateral geniculate nucleus, cortical neurophysiology, and spatial resolution in monkeys.

In Vivo Foveal Development Using Optical Coherence Tomography.

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 = 0.54 (P < 0.0001) and r = 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.

Choroidal thickness in childhood.

PURPOSE: We examined choroidal thickness (ChT) and its spatial distribution across the posterior pole in pediatric subjects with normal ocular health and minimal refractive error. METHODS: ChT was assessed using spectral domain optical coherence tomography (OCT) in 194 children aged 4 to 12 years, with spherical equivalent refractive errors between +1.25 and -0.50 diopters sphere (DS). A series of OCT scans were collected, imaging the choroid along 4 radial scan lines centered on the fovea (each separated by 45°). Frame averaging was used to reduce noise and enhance chorioscleral junction visibility. The transverse scale of each scan was corrected to account for magnification effects associated with axial length. Two independent masked observers segmented the OCT images manually to determine ChT at foveal center, and averaged across a series of perifoveal zones over the central 5 mm. RESULTS: The average subfoveal ChT was 330 ± 65 µm (range, 189-538 µm), and was influenced significantly by age (P = 0.04). The ChT of the 4- to 6-year-old age group (312 ± 62 µm) was significantly thinner compared to the 7- to 9-year-olds (337 ± 65 µm, P < 0.05) and bordered on significance compared to the 10- to 12-year-olds (341 ± 61 µm, P = 0.08). ChT also exhibited significant variation across the posterior pole, being thicker in more central regions. The choroid was thinner nasally and inferiorly compared to temporally and superiorly. Multiple regression analysis revealed age, axial length, and anterior chamber depth were associated significantly with subfoveal ChT (P < 0.001). CONCLUSIONS: ChT increases significantly from early childhood to adolescence. This appears to be a normal feature of childhood eye growth.

Blue-light reflectance imaging of macular pigment in infants and children.

PURPOSE: While the role of the macular pigment carotenoids in the prevention of age-related macular degeneration has been extensively studied in adults, comparatively little is known about the physiology and function of lutein and zeaxanthin in the developing eye. We therefore developed a protocol using a digital video fundus camera (RetCam) to measure macular pigment optical density (MPOD) and distributions in premature infants and in children. METHODS: We used blue light reflectance to image the macular pigment in premature babies at the time of retinopathy of prematurity (ROP) screening and in children aged under 7 years who were undergoing examinations under anesthesia for other reasons. We correlated the MPOD with skin carotenoid levels measured by resonance Raman spectroscopy, serum carotenoids measured by HPLC, and dietary carotenoid intake. RESULTS: We enrolled 51 infants and children ranging from preterm to age 7 years. MPOD correlated significantly with age (r = 0.36; P = 0.0142), with serum lutein + zeaxanthin (r = 0.44; P = 0.0049) and with skin carotenoid levels (r = 0.42; P = 0.0106), but not with dietary lutein + zeaxanthin intake (r = 0.13; P = 0.50). All premature infants had undetectable macular pigment, and most had unusually low serum and skin carotenoid concentrations. CONCLUSIONS: Our most remarkable finding is the undetectable MPOD in premature infants. This may be due in part to foveal immaturity, but the very low levels of serum and skin carotenoids suggest that these infants are carotenoid insufficient as a consequence of low dietary intake and/or severe oxidative stress. The potential value of carotenoid supplementation in the prevention of ROP and other disorders of prematurity should be a fruitful direction for further investigation.

Evaluation of normal human foveal development using optical coherence tomography and histologic examination.

OBJECTIVE: To assess outer retinal layer maturation during late gestation and early postnatal life using optical coherence tomography and histologic examination. METHODS: Thirty-nine participants 30 weeks' postmenstrual age or older were imaged using a handheld optical coherence tomography system, for a total of 102 imaging sessions. Foveal images from 16 participants (21 imaging sessions) were normal and evaluated for inner retinal excavation and the presence of outer retinal reflective bands. Reflectivity profiles of central, parafoveal, and parafoveal retina were extracted and were compared with age-matched histologic sections. RESULTS: The foveal pit morphologic structure in infants was generally distinguishable from that in adults. Reflectivity profiles showed a single hyperreflective band at the fovea in all the infants younger than 42 weeks' postmenstrual age. Multiple bands were distinguishable in the outer retina at the peri fovea by 32 weeks' postmenstrual age and at the fovea by 3 months' postterm. By 17 months' postnatal, the characteristic appearance of 4 hyperreflective bands was evident across the foveal region. These features are consistent with previous results from histologic examinations. A "temporal divot" was present in some infants, and the foveal pit morphologic structure and the extent of inner retinal excavation were variable. CONCLUSIONS: Handheld optical coherence tomography is a viable technique for evaluating neonatal retinas. In premature infants who do not develop retinopathy of prematurity, the foveal region seems to follow a developmental time course similar to that associated with in utero maturation. CLINICAL RELEVANCE: As pediatric optical coherence tomography becomes more common, a better understanding of normal foveal and macular development is needed. Longitudinal imaging offers the opportunity to track postnatal foveal development among preterm infants in whom poor visual outcomes are anticipated or to follow up treatment outcomes in this population.

Histologic development of the human fovea from midgestation to maturity.

PURPOSE: To describe the histologic development of the human central retina from fetal week (Fwk) 22 to 13 years. DESIGN: Retrospective observational case series. METHODS: Retinal layers and neuronal substructures were delineated on foveal sections of fixed tissue stained in azure II-methylene blue and on frozen sections immunolabeled for cone, rod, or glial proteins. Postmortem tissue was from 11 eyes at Fwk 20-27; 8 eyes at Fwk 28-37; 6 eyes at postnatal 1 day to 6 weeks; 3 eyes at 9 to 15 months; and 5 eyes at 28 months to 13 years. RESULTS: At Fwk 20-22 the fovea could be identified by the presence of a single layer of cones in the outer nuclear layer. Immunolabeling detected synaptic proteins, cone and rod opsins, and Müller glial processes separating the photoreceptors. The foveal pit appeared at Fwk 25, involving progressive peripheral displacement of ganglion cell, inner plexiform, and inner nuclear layers. The pit became wider and shallower after birth, and appeared mature by 15 months. Between Fwk 25 and Fwk 38, all photoreceptors developed more distinct inner and outer segments, but these were longer on peripheral than foveal cones. After birth the foveal outer nuclear layer became much thicker as cone packing occurred. Cone packing and neuronal migration during pit formation combined to form long central photoreceptor axons, which changed the outer plexiform layer from a thin sheet of synaptic pedicles into the thickest layer in the central retina by 15 months. Foveal inner and outer segment length matched peripheral cones by 15 months and was 4 times longer by 13 years. CONCLUSIONS: These data are necessary to understand the marked changes in human retina from late gestation to early adulthood. They provide qualitative and quantitative morphologic information required to interpret the changes in hyper- and hyporeflexive bands in pediatric spectral-domain optical coherence tomography images at the same ages.

Maturation of the human fovea: correlation of spectral-domain optical coherence tomography findings with histology.

PURPOSE: To correlate human foveal development visualized by spectral-domain optical coherence tomography (SDOCT) with histologic specimens. DESIGN: Retrospective, observational case series. METHODS: Morphology and layer thickness of retinal SDOCT images from 1 eye each of 22 premature infants, 30 term infants, 16 children, and 1 adult without macular disease were compared to light microscopic histology from comparable ages. RESULTS: SDOCT images correlate with major histologic findings at all time points. With both methods, preterm infants demonstrate a shallow foveal pit indenting inner retinal layers (IRL) and short, undeveloped foveal photoreceptors. At term, further IRL displacement forms the pit and peripheral photoreceptors lengthen; the elongation of inner and outer segments (IS and OS, histology) separates the IS band from retinal pigment epithelium. Foveal IS and OS are shorter than peripheral for weeks after birth (both methods). By 13 months, foveal cone cell bodies stack >6 deep, Henle fiber layer (HFL) thickens, and IS/OS length equals peripheral; on SDOCT, foveal outer nuclear layer (which includes HFL) and IS/OS thickens. At 13 to 16 years, the fovea is fully developed with a full complement of SDOCT bands; cone cell bodies >10 deep have thin, elongated, and tightly packed IS/OS. CONCLUSIONS: We define anatomic correlates to SDOCT images from normal prenatal and postnatal human fovea. OCT bands typical of photoreceptors of the adult fovea are absent near birth because of the immaturity of foveal cones, develop by 24 months, and mature into childhood. This validates the source of SDOCT signal and provides a framework to assess foveal development and disease.