No abstract

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 To assess retinal nerve fiber layer (RNFL) thickness at term-equivalent age in very preterm (<32 weeks gestational age) versus term-born infant cohorts, and compare very preterm infant RNFL thickness with brain anatomy and neurodevelopment. Design Cohort study. Methods RNFL was semi-automatically segmented (one eye per infant) in 57 very preterm and 50 term infants with adequate images from bedside portable, handheld spectral domain optical coherence tomography (Bioptigen, Inc., Research Triangle Park, NC) imaging at 37-42 weeks postmenstrual age. Mean RNFL thickness was calculated for the papillomacular bundle (−15° to + 15°) and temporal quadrant (−45° to +45°) relative to the fovea-optic nerve axis. Brain magnetic resonance imaging (MRI) scans clinically obtained in 26 very preterm infants were scored for global structural abnormalities by an expert masked to data except for age. Cognitive, language, and motor skills were assessed with Bayley Scales of Infant and Toddler Development-III (Pearson, San Antonio, TX) in 33 of the very preterm infants at 18-24 months corrected age. Results RNFL was thinner for very preterm versus term infants at the papillomacular bundle ([mean ± standard deviation] 61 ± 17 versus 72 ± 13 μm, p<0.001) and temporal quadrant (72 ± 21 versus 82 ± 16 μm, p=0.005). In very preterm infants, thinner papillomacular bundle RNFL correlated with higher global brain MRI lesion burden index (R2=0.35, p=0.001) and lower cognitive (R2=0.18, p=0.01) and motor (R2=0.17, p=0.02) scores. Relationships were similar for temporal quadrant. Conclusions Thinner RNFL in very preterm infants relative to term-born infants may relate to brain structure and neurodevelopment.

No abstract