Objective: To demonstrate optical coherence tomography for high-resolution, noninvasive imaging of the human retina. Optical coherence tomography is a new imaging technique analogous to ultrasound B scan that can provide cross-sectional images of the retina with micrometer-scale resolution. Design: Survey optical coherence tomographic examination of the retina, including the macula and optic nerve head in normal human subjects. Settings Research laboratory. Participants: Convenience sample of normal human subjects. Main Outcome Measures: Correlation of optical coherence retinal tomographs with known normal retinal anatomy. Results: Optical coherence tomographs can discriminate the cross-sectional morphologic features of the fovea and optic disc, the layered structure of the retina, and normal anatomic variations in retinal and retinal nerve fiber layer thicknesses with 10- μm depth resolution. Conclusion: Optical coherence tomography is a potentially useful technique for high depth resolution, cross-sectional examination of the fundus.

Optical Coherence Tomography of the Human Retina

Purpose Basal laminar deposit (BLamD) is a consistent finding in age-related macular degeneration (AMD). We quantified BLamD thickness, appearance, and topography in eyes of aged donors with and without AMD and evaluated its relationship to other components of the retinal pigment epithelium-basal lamina/Bruch's membrane (RPE-BL-BrM) complex. Methods Donor eyes (n = 132) were classified as normal (n = 54), early to intermediate AMD (n = 24), geographic atrophy (GA; n = 13), and neovascular AMD (NV; n = 41). In high-resolution histology, we assessed RPE, BLamD, and BrM thicknesses and phenotypes at 3309 predefined locations in the central (foveal and perifovea) and superior (perifoveal) sections. Pre-mortem optical coherence tomography (OCT) imaging of a 90-year-old woman was compared to postmortem histopathology. Results In non-atrophic areas of AMD eyes, the RPE-BLamD is thick (normal = 13.7 µm, early-intermediate = 16.8 µm, GA = 17.4 µm, NV = 18.7 µm), because the BLamD is thick (normal = 0.3 µm, early-intermediate = 5.5 µm, GA = 4.1 µm, NV = 5.3 µm). RPE layer thickness is similar across these stages. Disease-associated variants of BLamD (thick, late, basal mounds) cluster subfoveally. A thick BLamD is visible on OCT as a hyporeflective split in the RPE-BL-BrM complex. BrM is thin (3.5 µm) in NV (normal = 4.2 µm, early to intermediate = 4.4 µm, and GA = 4.2 µm). Conclusions The RPE-BL-BrM complex is thick in AMD, driven by the accumulation and expansion of BLamD rather than expansion of either three-layer BrM, RPE-BL, or RPE. BLamD is clinically appreciable by OCT in some patients as a non-neovascular "split RPE-BL-BrM complex" or "double-layer sign." BLamD may contribute toward the formation and progression of high-risk drusen yet also exhibit protective properties.

Measuring the Contributions of Basal Laminar Deposit and Bruch's Membrane in Age-Related Macular Degeneration.

Choriocapillaris: Fundamentals and advancements

We describe what are to our knowledge the first in vivo measurements of human retinal structure with optical coherence tomography. These images represent the highest depth resolution in vivo retinal images to date. The tomographic system, image-processing techniques, and examples of high-resolution tomographs and their clinical relevance are discussed.

In vivo retinal imaging by optical coherence tomography

Importance Sensitive outcome measures for disease progression are needed for treatment trials in geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Objective To quantify photoreceptor degeneration outside regions of GA in eyes with nonexudative AMD, to evaluate its association with future GA progression, and to characterize its spatio-temporal progression. Design, Setting, and Participants Monocenter cohort study (Directional Spread in Geographic Atrophy [NCT02051998]) and analysis of data from a normative data study at a tertiary referral center. One hundred fifty-eight eyes of 89 patients with a mean (SD) age of 77.7 (7.1) years, median area of GA of 8.87 mm2(IQR, 4.09-15.60), and median follow-up of 1.1 years (IQR, 0.52-1.7 years), as well as 93 normal eyes from 93 participants. Exposures Longitudinal spectral-domain optical coherence tomography (SD-OCT) volume scans (121 B-scans across 30° × 25°) were segmented with a deep-learning pipeline and standardized in a pointwise manner with age-adjusted normal data (z scores). Outer nuclear layer (ONL), photoreceptor inner segment (IS), and outer segment (OS) thickness were quantified along evenly spaced contour lines surrounding GA lesions. Linear mixed models were applied to assess the association between photoreceptor-related imaging features and GA progression rates and characterize the pattern of photoreceptor degeneration over time. Main Outcomes and Measures Association of ONL thinning with follow-up time (after adjusting for age, retinal topography [zscore], and distance to the GA boundary). Results The study included 158 eyes of 89 patients (51 women and 38 men) with a mean (SD) age of 77.7 (7.1) years. The fully automated B-scan segmentation was accurate (dice coefficient, 0.82; 95% CI, 0.80-0.85; compared with manual markings) and revealed a marked interpatient variability in photoreceptor degeneration. The ellipsoid zone (EZ) loss-to-GA boundary distance and OS thickness were prognostic for future progression rates. Outer nuclear layer and IS thinning over time was significant even when adjusting for age and proximity to the GA boundary (estimates of −0.16 μm/y; 95% CI, −0.30 to −0.02; and −0.17 μm/y; 95% CI, −0.26 to −0.09). Conclusions and Relevance Distinct and progressive alterations of photoreceptor laminae (exceeding GA spatially) were detectable and quantifiable. The degree of photoreceptor degeneration outside of regions of retinal pigment epithelium atrophy varied markedly between eyes and was associated with future GA progression. Macula-wide photoreceptor laminae thinning represents a potential candidate end point to monitor treatment effects beyond mere GA lesion size progression.

Progression of Photoreceptor Degeneration in Geographic Atrophy Secondary to Age-related Macular Degeneration.

Purpose To develop high-speed, extended-range, ultrahigh-resolution spectral-domain optical coherence tomography (UHR SD-OCT) and demonstrate scan protocols for clinical retinal imaging. Methods A UHR SD-OCT operating at 840-nm with 150-nm bandwidths was developed. The axial imaging range was extended by dynamically matching reference arm length to the retinal contour during acquisition. Two scan protocols were demonstrated for imaging healthy participants and patients with dry age-related macular degeneration. A high-definition raster protocol with intra-B-scan reference arm length matching (ReALM) was used for high-quality cross-sectional imaging. A cube volume scan using horizontal and vertical rasters with inter-B-scan ReALM and software motion correction was used for en face and cross-sectional imaging. Linear OCT signal display enhanced visualization of outer retinal features. Results UHR SD-OCT was demonstrated at 128- and 250-kHz A-scan rates with 2.7 µm axial resolution and a 1.2-mm, 6-dB imaging range in the eye. Dynamic ReALM was used to maintain the retina within the 6-dB imaging range over wider fields of view. Outer retinal features, including the rod and cone interdigitation zones, retinal pigment epithelium, and Bruch's membrane were visualized and alterations observed in age-related macular degeneration eyes. Conclusions Technological advances and dynamic ReALM improve the imaging performance and clinical usability of UHR SD-OCT. Translational relevance These advances should simplify clinical imaging workflow, reduce imaging session times, and improve yield of high quality images. Improved visualization of photoreceptors, retinal pigment epithelium, and Bruch's membrane may facilitate diagnosis and monitoring of age-related macular degeneration and other retinal diseases.

High-Speed, Ultrahigh-Resolution Spectral-Domain OCT with Extended Imaging Range Using Reference Arm Length Matching.

A Framework for Multiscale Quantitation of Relationships Between Choriocapillaris Flow Impairment and Geographic Atrophy Growth

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High-Speed, Ultrahigh-Resolution Spectral-Domain OCT with Extended Imaging Range Using Reference Arm Length Matching.

A Framework for Multiscale Quantitation of Relationships Between Choriocapillaris Flow Impairment and Geographic Atrophy Growth