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Purpose To describe the histological 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 9–15 months; and 5 eyes at 28 months-13 years. Results At Fwk20–22 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 Muller glial processes separating the photoreceptors. The foveal pit appeared at Fwk25, 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 15months. Between Fwk25 and Fwk38, 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× 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 morphological information required to interpret the changes in hyper- and hypo-reflexive bands in pediatric spectral domain optical coherence tomography (SDOCT) images at the same ages.

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.

Purpose To evaluate and quantify visual function metrics to be used as predictors of AMD progression and visual acuity (VA) loss in patients with early and intermediate AMD. Design Baseline data of observational, cross-sectional, prospective study. Methods 101 patients were enrolled at Duke Eye Center: 80 patients with AMD age-related eye disease study (AREDS) stage 2 (N=33) and stage 3 (N=47) and 21 age-matched, normal controls. A dilated retinal examination, macular pigment optical density measurements, and several functional assessments: best-corrected VA, mesopic microperimety with eye tracking (MAIA), dark adaptometry (AdaptDx), low luminance VA (LLVA) (standard using log 2.0 neutral density filter and computerized method) and cone contrast test (CCT) (Innova Systems Inc) were performed. Low luminance deficit (LLD) was defined as the difference in numbers of letters read at standard vs. low luminance. Group comparisons were performed to evaluate differences between the control and the AREDS 2 and AREDS 3 groups using two-sided significance tests. Results Functional measures that significantly distinguished between normal and AREDS3 were standard and computerized (0.5 cd/m2) LLVA, percent reduced threshold and average threshold on microperimetry, CCTs, and rod intercept on dark adaptation (p < 0.05). The AREDS 3 group demonstrated deficits in microperimetry reduced threshhold, computerized LLD2 and dark adaptation rod intercept (p < 0.05) relative to AREDS 2. Conclusions and Relevance Our study suggests that LLVA, MAIA microperimetry, CCT and dark adaptation may serve as functional measures of AMD progression.

Photoreceptor inner and outer segment development in VPT infants appears delayed when compared to term infants, and the photoreceptor RPE junction remains immature in all infants at TEA. Delayed maturation of photoreceptors could contribute to differences in visual function in some VPT infants.

PURPOSE In the treatment of uveal melanomas, the optimal prescribed dose to maximize disease control, but minimize radiation-related complications is unknown. Historically our institution has treated uveal melanomas to doses less than 85 Gy to the tumor apex even if the apex was less than 5mm in height. Here, we investigate how tumor control and visual outcomes are affected by the radiation dose at the tumor apex. METHODS AND MATERIALS A retrospective review was performed to evaluate patients treated for uveal melanoma with Iodine-125 plaques between 1988 and 2010. Radiation dose is reported as dose to tumor apex and dose to 5 mm. Primary end points included time to local failure, distant failure, and death. Secondary end points included eye preservation, visual acuity, and radiation-related complications. Univariate and multivariate analyses were performed to determine association between radiation dose and the end point variables. RESULTS One hundred ninety patients with sufficient data to evaluate the end points were included. The 5 year local control (LC) rate was 91%. The 5 year distant metastases (DM) rate was 10%. The 5 year overall survival (OS) rate was 84%. There were no differences in outcome (LC, DM, OS) when dose was stratified by apex dose quartile (<69 Gy, 69–81 Gy, 81–89 Gy, >89 Gy). However, increasing apex dose and dose to 5 mm depth were correlated with greater visual acuity loss (p=0.02, p=0.0006), worse final visual acuity (p=0.02, p<0.0001) and radiation complications (p<0.0001, p=0.0009). In addition, enucleation rates were worse with increasing quartiles of dose to 5 mm (p=0.0001). CONCLUSIONS Doses at least as low as 69 Gy prescribed to the tumor apex achieve rates of local control, distant metastasis free survival, and overall survival that are similar to radiation doses of 85 Gy to the tumor apex, but with improved visual outcomes.

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