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.

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Purpose Structural and compositional heterogeneity within drusen, composed of lipid, carbohydrates, and proteins, have been previously described. We sought to detect and define phenotypic patterns of drusen heterogeneity in the form of optical coherence tomography–reflective drusen substructures (ODS) and examine their associations with age-related macular degeneration (AMD)-related features and AMD progression. Design Retrospective analysis in a prospective study. Participants Patients with intermediate AMD (n = 349) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) ancillary spectral domain optical coherence tomography (SD OCT) study. Methods Baseline SD OCT scans of 1 eye per patient were analyzed for presence of ODS. Cross-sectional and longitudinal associations of ODS presence with AMD-related features visible on SD OCT and color photographs, including drusen volume, geographic atrophy (GA), and preatrophic features, were evaluated for the entire macular region. Similar associations were also made locally within a 0.5-mm diameter region around individual ODS and corresponding control region without ODS in the same eye. Main Outcome Measures Preatrophy SD OCT changes and GA, central GA, and choroidal neovascularization (CNV) from color photographs. Results Four phenotypic subtypes of ODS were defined: low reflective cores, high reflective cores, conical debris, and split drusen. Of the 349 participants, there were 307 eligible eyes and 74 (24%) had at least 1 ODS. The ODS at baseline were associated with (1) greater macular drusen volume at baseline (P < 0.001), (2) development of preatrophic changes at year 2 (P = 0.001–0.01), and (3) development of macular GA (P = 0.005) and preatrophic changes at year 3 (P = 0.002–0.008), but not development of CNV. The ODS at baseline in a local region were associated with (1) presence of preatrophy changes at baseline (P = 0.02-0.03) and (2) development of preatrophy changes at years 2 and 3 within the region (P = 0.008-0.05). Conclusions Optical coherence tomography–reflective drusen substructures are optical coherence tomography–based biomarkers of progression to GA, but not to CNV, in eyes with intermediate AMD. Optical coherence tomography–reflective drusen substructures may be a clinical entity helpful in monitoring AMD progression and informing mechanisms in GA pathogenesis.

Purpose To evaluate relationships between age-related macular degeneration (AMD) morphology on spectral domain optical coherence tomography (SDOCT) and visual function. Design Cross-sectional, observational. Methods From the Alabama Study on Early AMD baseline visit, visual acuity, cone-mediated sensitivity (Humphrey Field Analyzer, Carl Zeiss Meditec, Dublin, CA), rod-mediated dark adaptation (AdaptDx, MacuLogix, Hummelstown, PA), and SDOCT (Spectralis, Heidelberg Engineering, Germany) were obtained in one eye per subject with No Apparent Retinal Aging (N=15), Normal Aging (N=15), Early AMD (N=15), and Intermediate (N=46) AMD. The volumes of retinal pigment epithelium (RPE)-drusen-complex, RPE-drusen-complex abnormal thinning, RPE-drusen-complex abnormal thickening and inner and outer retina were calculated in specified regions using semi-automated SDOCT segmentation. Results Better cone-mediated sensitivity was associated with greater RPE-drusen-complex volume (r=0.34, p<0.001) and less RPE-drusen-complex abnormal thinning volume (r=-0.31, p=0.003). Longer rod-mediated dark adaptation time, the duration for rod-mediated sensitivity to recover from photo-bleach exposure, correlated with lower RPE-drusen-complex volume (r=-0.34, p=0.005) and greater RPE-drusen-complex abnormal thinning volume (r=0.280, p=0.023). In 19 eyes with subretinal drusenoid deposits (SDD) versus 47 eyes without SDD, rod-mediated dark adaptation time was longer (mean ±SD 13.5 ±7.0 versus 10.2 ±3.1 minutes, p=0.004), RPE-drusen-complex abnormal thinning volume was greater (p<0.0001), and visual acuity and cone sensitivity did not differ. Conclusion Decreased function relates to structural markers on SDOCT in AMD. Because the RPE-drusen-complex includes the interdigitation of outer segments and RPE apical processes and SDD in eyes with AMD, slower dark adaptation might be related to structural abnormalities of the RPE, the RPE-photoreceptor interface, or both.

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.