Linking OCT, Angiographic, and Photographic Lesion Components in Neovascular Age-Related Macular Degeneration.

PURPOSE: To develop methods to make precise comparisons of specific retinal features between and within spectral-domain (SD) OCT images, color fundus photography (CFP) images, and fluorescein angiography (FA) images in eyes treated with anti-vascular endothelial growth factor (VEGF) agents for neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective study. PARTICIPANTS: Patients with good study-eye images at the 104-week visit in the Comparison of Age-Related Macular Degeneration Treatments Trials. METHODS: Graders reviewed CFP and FA images and delineated areas of fibrotic or nonfibrotic scar and geographic atrophy (GA) or non-GA. Other graders reviewed SD-OCT images and delineated retinal and subretinal lesion characteristics. Using newly developed custom software and graphic user interfaces, the presence and thickness of each feature at each pixel on the en face view was determined. MAIN OUTCOME MEASURES: Spectral-domain OCT findings versus CFP and FA lesion components from regional overlays. RESULTS: Per-eye distribution and thickness of SD-OCT features within CFP- and FA-established areas of scar and atrophy can be determined precisely, can be displayed in multiple formats, and can be extracted into pixel-specific data sets. These methods enable statistical analysis of imaging results within eyes and across eyes of different patients. For example, photoreceptor loss, subretinal lesion material, and thicknesses of photoreceptor layer and subretinal material across those SD-OCT features can be related precisely to CFP and FA regions of scar or atrophy. CONCLUSIONS: Methods to integrate qualitative and quantitative retinal and subretinal changes to coincide with photographic and angiographic designations of the nAMD lesion areas and sequelae are integral for accurate assessments of posttreatment retinal morphologic features. These may lead to better understanding of disease progression and improved treatment strategies.

Relating Retinal Morphology and Function in Aging and Early to Intermediate Age-related Macular Degeneration Subjects.

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, rod-mediated dark adaptation, and SDOCT were obtained in 1 eye per subject with no apparent retinal aging (n = 15), normal aging (n = 15), early AMD (n = 15), and intermediate AMD (n = 46). 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 < .001) and less RPE-drusen complex abnormal thinning volume (r = -0.31, P = .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 = .005) and greater RPE-drusen complex abnormal thinning volume (r = 0.280, P = .023). In 19 eyes with subretinal drusenoid deposits (SDD) vs 47 eyes without SDD, rod-mediated dark adaptation time was longer (mean ± SD 13.5 ± 7.0 vs 10.2 ± 3.1 minutes, P = .004), RPE-drusen complex abnormal thinning volume was greater (P < .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.

Drusen Volume and Retinal Pigment Epithelium Abnormal Thinning Volume Predict 2-Year Progression of Age-Related Macular Degeneration.

PURPOSE: To analyze the value of novel measures of retinal pigment epithelium-drusen complex (RPEDC) volume to predict 2-year disease progression of intermediate age-related macular degeneration (AMD). DESIGN: Prospective, observational study. PARTICIPANTS: Three hundred forty-five AMD and 122 non-AMD participants enrolled in the Age Related Eye Disease Study 2 Ancillary Spectral-Domain (SD) Optical Coherence Tomography (OCT) study. METHODS: High-density SD OCT macular volumes were obtained at yearly study visits. The RPEDC abnormal thickening (henceforth, OCT drusen) and RPEDC abnormal thinning (RAT) volumes were generated by semiautomated segmentation of total RPEDC within a 5-mm-diameter macular field. MAIN OUTCOME MEASURES: Volume change and odds ratio (OR) with 95% confidence intervals (CI) for progression to advanced AMD with choroidal neovascularization (CNV) or central geographic atrophy (GA). RESULTS: Complete volumes were obtained in 265 and 266 AMD eyes and in 115 and 97 control eyes at baseline and at year 2, respectively. In AMD eyes, mean (standard deviation) OCT drusen volume increased from 0.08 mm(3) (0.16 mm(3)) to 0.10 mm(3) (0.23 mm(3); P < 0.001), and RAT volume increased from 8.3 × 10(-4) mm(3) (20.8 × 10(-4) mm(3)) to 18.4 × 10(-4) mm(3) (46.6 × 10(-4) mm(3); P < 0.001). Greater baseline OCT drusen volume was associated with 2-year progression to CNV (P = 0.002). Odds of developing CNV increased by 31% for every 0.1-mm(3) increase in baseline OCT drusen volume (OR, 1.31; 95% CI, 1.06-1.63; P = 0.013). Greater baseline RAT volume was associated with significant 2-year increase in RAT volume (P < 0.001), noncentral GA (P < 0.001), and progression to central GA (P < 0.001). Odds of developing central GA increased by 32% for every 0.001-mm(3) increase in baseline RAT volume (OR, 1.32; 95% CI, 1.14-1.53; P < 0.001). In non-AMD eyes, all volumes were significantly lower than AMD eyes and showed no significant 2-year change. CONCLUSIONS: Macular OCT drusen and RAT volumes increased significantly in AMD eyes over 2 years. These quantitative SD OCT biomarkers predict 2-year AMD progression and may serve as useful biomarkers for future clinical trials.

Thinner Retinal Nerve Fiber Layer in Very Preterm Versus Term Infants and Relationship to Brain Anatomy and Neurodevelopment.

PURPOSE: To assess retinal nerve fiber layer (RNFL) thickness at term-equivalent age in very preterm (<32 weeks gestational age) vs 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 (1 eye per infant) in 57 very preterm and 50 term infants with adequate images from bedside portable, handheld spectral-domain optical coherence tomography imaging at 37-42 weeks postmenstrual age. Mean RNFL thickness was calculated for the papillomacular bundle (-15 degrees to +15 degrees) and temporal quadrant (-45 degrees to +45 degrees) 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 in 33 of the very preterm infants at 18-24 months corrected age. RESULTS: RNFL was thinner for very preterm vs term infants at the papillomacular bundle ([mean ± standard deviation] 61 ± 17 vs 72 ± 13 µm, P < .001) and temporal quadrant (72 ± 21 vs 82 ± 16 µm, P = .005). In very preterm infants, thinner papillomacular bundle RNFL correlated with higher global brain MRI lesion burden index (R(2) = 0.35, P = .001) and lower cognitive (R(2) = 0.18, P = .01) and motor (R(2) = 0.17, P = .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.

INTRAOPERATIVE SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING AFTER INTERNAL LIMITING MEMBRANE PEELING IN IDIOPATHIC EPIRETINAL MEMBRANE WITH CONNECTING STRANDS.

PURPOSE: To report the intraoperative optical coherence tomography findings in idiopathic epiretinal membrane (ERM) with connecting strands and to describe the postoperative outcomes. METHODS: A retrospective, case series study within a prospective observational intraoperative optical coherence tomography imaging study was performed. Epiretinal membranes with connecting strands were characterized on preoperative spectral domain optical coherence tomography images and assessed against corresponding intraoperative (after internal limiting membrane [ILM] peeling) and postoperative spectral domain optical coherence tomography images. RESULTS: Eleven locations of the connecting strands in 7 eyes were studied. The connecting strands had visible connections from the inner retinal surface to the ERM in all locations, and the reflectivity was moderate in 8 locations and high in 3 locations. After ERM and ILM peeling, disconnected strands were identified in all of the intraoperative optical coherence tomography images. The reflectivity of the remaining intraoperative strands was higher than that of the preoperative lesions and appeared as "finger-like" and branching projections. The remaining disconnected lesions were contiguous with the inner retinal layers. Postoperatively, the intraoperative lesions disappeared completely in all locations, and recurrent formation of ERM was not identified in any eyes. CONCLUSION: In ERM eyes with connecting strands, intraoperative spectral domain optical coherence tomography imaging showed moderately to highly reflective sub-ILM finger-like lesions that persist immediately after membrane and ILM peeling. Postoperatively, the hyperreflective lesions disappeared spontaneously without localized nerve fiber layer loss. The sub-ILM connecting strands may represent glial retinal attachments.

Assessment of retinal nerve fiber layer thickness in healthy, full-term neonates.

PURPOSE: To measure average retinal nerve fiber layer (RNFL) thicknesses in healthy, full-term neonates. DESIGN: Descriptive research to develop normative data. METHODS: Healthy infants born between 37 and 42 weeks postmenstrual age were imaged with hand-held spectral-domain optical coherence tomography. A custom script segmented the RNFL; the fovea and optic nerve center were manually selected. A second script measured the average RNFL thickness along the papillomacular bundle, defined as the arc from -15 degrees to +15 degrees on the axis from the optic nerve to fovea, with radii of 1.1, 1.3, 1.5, and 1.7 mm from the center of the optic disc. Shapiro-Wilk W tests assessed these measurements for normality to determine the age-appropriate radial distance for subsequent analyses. Average RNFL thicknesses for four temporal 45-degree sectors (superior temporal, temporal superior, temporal inferior, and inferior temporal) and the temporal quadrant were calculated and compared to demographic parameters for all infants. RESULTS: Fifty full-term infants were adequately imaged for RNFL analysis. RNFL thicknesses at 1.5 mm radial distance from the optic nerve were the most normally distributed. While there was a trend toward greater mean superior temporal RNFL thickness for both black and Hispanic vs white infants (128 ± 27 µm, 124 ± 30 µm, and 100 ± 19 µm, respectively, P = .04 for both comparisons), there were no other significant differences noted in RNFL thicknesses by race, sex, gestational age, or birth weight. CONCLUSIONS: We present RNFL thickness measurements for healthy, full-term infants that may serve as normative data for future analyses.