To collect a normative database of macular thickness, retinal nerve fiber layer (RNFL) thicknesses, and optic nerve topography in the healthy eyes of children aged 3 to 17 years using optical coherence tomography (OCT) measurements.Methods: Scans were obtained for 286 healthy children (black, 114; white, 154; other, 18). Each child had a dilated eye examination, an axial length measurement using the IOL Master (Carl Zeiss Meditec, Dublin, California), and OCT measurements using the fast macular map, fast RNFL thickness, and fast optic disc protocols of the Stratus OCT (OCT-3; Carl Zeiss Meditec).Results: Black children had smaller macular volume and foveal thickness, larger RNFL thickness, and larger cup-

Objective To evaluate the association of subretinal hyper-reflective material (SHRM) with visual acuity (VA), geographic atrophy (GA) and scar in the Comparison of Age related Macular Degeneration Treatments Trials (CATT) Design Prospective cohort study within a randomized clinical trial. Participants The 1185 participants in CATT. Methods Participants were randomly assigned to ranibizumab or bevacizumab treatment monthly or as-needed. Masked readers graded scar and GA on fundus photography and fluorescein angiography images, SHRM on time domain (TD) and spectral domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1mm2, or outside the center 1mm2 were obtained on SD-OCT images at 56 (n=76) and 104 (n=66) weeks. VA was measured by certified examiners. Main Outcome Measures SHRM presence, location and size, and associations with VA, scar, and GA. Results Among all CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than eyes with SHRM that resolved (64% vs. 31%; p<0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n=76) and 104 (n=66), mean [SE] VA letter score was 73.5 [2.8], 73.1 [3.4], 65.3 [3.5], and 63.9 [3.7] when SHRM was absent, present outside the central 1mm2, present within the central 1mm2 but not the foveal center, or present at the foveal center (p=0.02). SHRM was present at the foveal center in 43 (30%), within the central 1mm2 in 21 (15%) and outside the central 1mm2 in 19 (13%). When SHRM was present, the median maximum height in microns under the fovea, within the central 1 mm2 including the fovea and anywhere within the scan was 86; 120; and 122, respectively. VA was decreased with greater SHRM height and width (p<0.05). Conclusions SHRM is common in eyes with NVAMD and often persists after anti-VEGF treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM height and width were associated with worse VA. SHRM is an important morphological biomarker in eyes with NVAMD.

Inherited optic neuropathies include complex phenotypes, mostly driven by mitochondrial dysfunction. We report an optic atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with mitochondrial DNA (mtDNA) depletion without accumulation of multiple deletions. By whole-exome sequencing, we identified mutations affecting the mitochondrial single-strand binding protein (SSBP1) in 4 families with dominant and 1 with recessive inheritance. We show that SSBP1 mutations in patient-derived fibroblasts variably affect the amount of SSBP1 protein and alter multimer formation, but not the binding to ssDNA. SSBP1 mutations impaired mtDNA, nucleoids, and 7S-DNA amounts as well as mtDNA replication, affecting replisome machinery. The variable mtDNA depletion in cells was reflected in severity of mitochondrial dysfunction, including respiratory efficiency, OXPHOS subunits, and complex amount and assembly. mtDNA depletion and cytochrome c oxidase-negative cells were found ex vivo in biopsies of affected tissues, such as kidney and skeletal muscle. Reduced efficiency of mtDNA replication was also reproduced in vitro, confirming the pathogenic mechanism. Furthermore, ssbp1 suppression in zebrafish induced signs of nephropathy and reduced optic nerve size, the latter phenotype complemented by WT mRNA but not by SSBP1 mutant transcripts. This previously unrecognized disease of mtDNA maintenance implicates SSBP1 mutations as a cause of human pathology.

The reproducibility of Spectralis spectral-domain-OCT were very good for both RNFL and macular thickness measurements in glaucoma/glaucoma suspect eyes of adult and pediatric subjects.

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We propose a clinical algorithm that is highly predictive for a positive TAB and can be valuable in the evaluation process of suspected cases of GCA.

Purpose Evaluate effects of prematurity on early optic nerve (ON) development and potential utility of ON parameters as indicators of central nervous system (CNS) development and pathology. Design Prospective cross-sectional and longitudinal study. Participants and Controls Forty-four preterm infants undergoing retinopathy of prematurity (ROP) screening and fifty-two term infants. Methods We analyzed optic nerves from portable handheld spectral domain optical coherence tomography (SDOCT) images (Bioptigen Inc., Research Triangle Park, NC) of 44 preterm and 52 term infants. The highest quality ON scan from either eye was selected for quantitative analysis. Longitudinal analysis was performed at both 31–36 and 37–42 weeks postmenstrual age (PMA). Preterm ON parameters were also assessed for correlation with indicators of cognitive, language and motor development, and CNS pathology. Main Outcome Measures Vertical cup diameter (vCupDiam), disc diameter (vDiscDiam), cup-to-disc ratio (vC:D), cup depth, and indicators of neuro-cognitive development and CNS pathology. Results At 37–42 weeks PMA, preterm infants had larger vCupDiam and vC:D than term infants (908 vs. 700 μm, p<0.001; 0.68 vs. 0.53 μm, p<0.001), while cup depth and vDiscDiam were not significantly different. Longitudinal changes (n=26 preterm eyes, mean interval 4.7 weeks) in vDiscDiam and in vC:D were an increase of 74 μm (p=0.008) and decrease of 0.05 (p=0.015), respectively. In preterm infants (n=44), periventricular leukomalacia was associated with larger vCupDiam (1084 vs. 828 μm, p=0.005) and vC:D (0.85 vs. 0.63, p<0.001), post-hemorrhagic hydrocephalus was associated with shallower cup (331 vs. 456 μm, p=0.030), and clinical magnetic resonance imaging (MRI) was associated with larger vC:D (0.73 vs. 0.64, p=0.023). In 23 preterm infants with Bayley Scales of Infant Development scores, larger vC:D was associated with lower cognitive scores (p=0.049). Conclusions This is the first analysis of ON parameters in premature infants using SDOCT. It demonstrated that by age of “term birth,” vCupDiam and vC:D are larger in preterm infants who were screened for ROP than in term infants. In this prospective pilot study, ON parameters in these preterm infants appear to weakly associate with CNS pathology and future cognitive development. Future prospective studies with larger numbers are necessary before further conclusions can be made.

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