Objective To define quantitative indicators for the presence of intermediate age-related macular degeneration (AMD) via spectral-domain optical coherence tomography (SD-OCT) imaging of older adults. Design Evaluation of diagnostic test and technology. Participants and Controls One eye from 115 elderly subjects without AMD and 269 subjects with intermediate AMD from the Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT Study. Methods We semiautomatically delineated the retinal pigment epithelium (RPE) and RPE drusen complex (RPEDC, the axial distance from the apex of the drusen and RPE layer to Bruch's membrane) and total retina (TR, the axial distance between the inner limiting and Bruch's membranes) boundaries. We registered and averaged the thickness maps from control subjects to generate a map of “normal” non-AMD thickness. We considered RPEDC thicknesses larger or smaller than 3 standard deviations from the mean as abnormal, indicating drusen or geographic atrophy (GA), respectively. We measured TR volumes, RPEDC volumes, and abnormal RPEDC thickening and thinning volumes for each subject. By using different combinations of these 4 disease indicators, we designed 5 automated classifiers for the presence of AMD on the basis of the generalized linear model regression framework. We trained and evaluated the performance of these classifiers using the leave-one-out method. Main Outcome Measures The range and topographic distribution of the RPEDC and TR thicknesses in a 5-mm diameter cylinder centered at the fovea. Results The most efficient method for separating AMD and control eyes required all 4 disease indicators. The area under the curve (AUC) of the receiver operating characteristic (ROC) for this classifier was >0.99. Overall neurosensory retinal thickening in eyes with AMD versus control eyes in our study contrasts with previous smaller studies. Conclusions We identified and validated efficient biometrics to distinguish AMD from normal eyes by analyzing the topographic distribution of normal and abnormal RPEDC thicknesses across a large atlas of eyes. We created an online atlas to share the 38 400 SD-OCT images in this study, their corresponding segmentations, and quantitative measurements. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

The automatic algorithm accurately and reproducibly segmented three retinal boundaries in images containing drusen and GA. This automatic approach can reduce time and labor costs and yield objective measurements that potentially reveal quantitative RPE changes in longitudinal clinical AMD studies. (ClinicalTrials.gov number, NCT00734487.).

Purpose To determine the dynamic morphological development of the human fovea in-vivo utilizing portable spectral domain optical coherence tomography (SDOCT). Design Prospective, observational case series. Paticipants 31 prematurely born neonates, nine children and nine adults. Methods Sixty-two neonates were enrolled in this study. SDOCT imaging was performed after examination for retinopathy of prematurity (ROP) at the bedside in non-sedated infants ages 31-41 weeks post-menstrual-age PMA (PMA=gestational age in weeks + chronological age) and at outpatient follow-up ophthalmic examinations. Thirty-one neonates met eligibility criteria. Nine children and nine adults without ocular pathology served as control groups. Semi-automatic retinal layer segmentation was performed. Central foveal thickness (CFT), foveal to parafoveal (FP) ratio (CFT divided by thickness 1000 μm from the foveal center), and 3D thickness maps were analyzed. Main Outcomes Measures In-vivo determination of foveal morphology, layer segmentation, analysis of sub-cellular changes, spatio-temporal layer shifting. Results In contrast to the adult fovea, we observed several signs of immaturity in the neonates: a shallow foveal pit, persistence of inner retinal layers (IRL), and a thin photoreceptor layer (PRL) that was thinnest at the foveal center. Three-dimensional mapping showed displacement of retinal layers out of the foveal center as the fovea matured and the progressive formation of the inner/outer segment band in the opposite direction. The FP-IRL ratios decreased as IRL migrated prior to term and minimally after that, while FP-PRL ratios increased as PRL subcellular elements formed closer to term and into childhood. A surprising finding was the presence of cystoid macular edema in 58% of premature neonates which appeared to affect inner foveal maturation. Conclusions This study provides the first view into development of living cellular layers of the human retina and of subcellular specialization at the fovea in premature infant eyes using portable spectral domain optical coherence tomography. Our work establishes a framework of the timeline of human foveal development, allowing us to identify unexpected retinal abnormalities that may provide new keys to disease activity, and provide a method for mapping of foveal structures from infancy to adulthood that may be integral in future studies of vision and visual cortex development.

Purpose Drusen and migrating retinal pigment epithelium have been associated with hyperreflective foci (HF) detected by spectral domain optical coherence tomography (SDOCT). This study sought to quantify the change in intraretinal HF distribution and its correlation with age-related macular degeneration (AMD) disease progression. Design Prospective observational study from the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT Study. Participants Patients (n = 299) with one enrolled eye with intermediate AMD and baseline SDOCT, followed by SDOCT imaging at 1-year and 2-year visits. Methods The number and location of HF were scored in SDOCT scans of all 299 eyes. The change in transverse (horizontal) and axial (vertical) distribution of HF in the macula were evaluated with pairwise signed rank tests. Two-year inner retinal HF migration was determined by the change in HF weighted axial distribution score (AxD) calculated for each eye. The correlation of HF with SDOCT features of AMD progression was evaluated with logistic regression analysis. Main Outcome Measures Mean change in number of HF, transverse and axial distribution of HF in the macula, and the AxD per eye. Results In 299 study eyes, the 2-year increase in the number of HF (p < 0.001) and AxD (p < 0.001) per eye represented longitudinal proliferation and shift to inner retinal layers, respectively. Eyes with geographic atrophy (GA) at 2 years were correlated with presence of baseline HF (p < 0.001; odds ratio [OR], 4.72; 95% confidence interval [CI], 2.43–9.80), greater number of baseline HF (p < 0.001; OR, 1.61 per HF; 95% CI, 1.32–2.00) and greater baseline AxD (p < 0.001; OR, 1.58 per AxD point; 95% CI, 1.29– 1.95). Conclusions Proliferation and inner retinal migration of SDOCT HF occurred during follow-up in eyes with intermediate AMD. These characteristics were associated with greater incidence of GA at year 2; therefore, SDOCT HF proliferation and migration may serve as biomarkers for AMD progression.

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.